mtDNA及GNB3基因多态性与新疆和田地区维吾尔族自然长寿的关联研究
|
摘要
背景
“健康与长寿”是生命科学永恒的主题,是21世纪人类最重要的奋斗目标和研究方向之一。那么,人为什么会衰老呢?衰老归因于发育、遗传失误、环境、疾病以及与生俱来的衰老进程(inborn aging process,IAP)。在衰老的研究中涉及对寿命的描述,其指标分为平均寿命和最大寿命。平均寿命决定人们对寿命的期望值。平均寿命与公共卫生状况和社会健康护理水平有关。最大寿命也就是寿命的极限,并不随公共卫生水平而改变。如何抵御或延缓衰老,达到人类应拥有的自然寿命,各国科学家从不同的角度提出了多种不同机制和理论,涉及到氧化应激、能量代谢、信号转导途径、免疫系统等多个系统的多种机制,而这些机制间又相互影响和作用,并在不同程度上受到遗传的影响。识别长寿相关生物学标记对深入理解其携带者免受常见疾病侵袭和/或衰老进程减慢的机制具有重要意义。目前,与炎症和免疫相关的基因、胰岛素/胰岛素样生长因子(insulin-like growth factor-1,IGF-1)信号途径、脂代谢相关基因以及氧化应激相关基因等成为研究热点,而线粒体基因组也逐渐成为研究的新方向。
百岁老人代表着寿命的极端情况,是进行人类长寿研究最佳的人群。新疆和田地区维吾尔族百岁老人数量和相对比例均高于全国平均水平,是世界四大长寿区之一。并且由于环境、生活特点及风俗习惯,形成了特殊的遗传隔离群,因此被称之为自然长寿人群,是长寿遗传学研究的难得资源。
长寿的遗传学研究方法,除常用的比较长寿者和对照人群之间单个多态性基因型分布的研究方法外,连锁不平衡和单倍型分析逐渐成为研究寿命这一受多基因及基因环境相互作用共同控制的复杂表型更为有效的遗传研究方法,对关联分析尤其复杂疾病的关联研究极为有用。
目的
探讨线粒体DNA(mitochondrial DNA,mtDNA)5178A/C、10398G/A多态性及其单倍型和G蛋白β3亚单位(G protein beta3 subunit,GNB3)基因C825T多态性与新疆和田地区维吾尔族自然长寿之间的关系。
方法
新疆和田地区275例研究对象均为和田地区常住居民,分为以下三组:165名年龄90岁以上的健康维吾尔族自然长寿个体分为百岁组(年龄≥100岁)65例,长寿组(年龄≥90岁、<100岁)100例,以112名地域、民族、性别相匹配的无长寿家族史,在75岁前自然死亡的个体为对照,进行流行病学调查。测定身高、体重、收缩压(systolic blood pressure,SBP)和舒张压(diastolic blood pressure,DBP)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、载脂蛋白A(apolipoprotein A,ApoA)和血糖(blood glucose,BG)水平。提取白细胞基因组DNA,分别采用PCR(polymerase chain reaction)、PCR-限制片段长度多态性(PCR-restriction fragment length polymorphism,PCR-RFLP)和PCR直接测序等技术对mtDNA 5178A/C、10398G/A多态性和GNB3基因C825T多态性进行基因分型,并进行单倍型分析。
结果
研究显示,mtDNA5178A/C和10398G/A多态性分析结果显示,百岁组和长寿组5178A等位基因和10398G等位基因频率较对照组明显增加。而百岁组和长寿组比较5178A等位基因和10398G等位基因频率分布无统计学意义。这与日本人群中的研究报告结果一致。我们同样发现,在百岁组5178AA与10398GG基因型组合明显高于对照组。我们认为线粒体DNA 5178AA及10398GG基因型与新疆和田地区维吾尔族自然长寿关联,而5178CC及10398AA基因型则可能是影响长寿的不利因素。单倍型分析显示每组有四种基因型组合,所有基因型组合频率分布在百岁组和长寿组中无统计学意义。然而,与对照组比较,百岁组和长寿组中mtDNA5178A/ 10398G基因型(A-G单倍型)组合明显高于对照组。细胞质基因多态性与长寿相关的诸多研究结果表明长寿与性别关联。但在本项调查中,我们对mtDNA5178A/C和10398G/A分析的结果显示其等位基因频率未发现性别差异。
对GNB3基因多态性的研究显示,在百岁组和对照组间,GNB3 825C/T的基因型和等位基因频率分布均具有统计学意义。其中在百岁组中CC基因型的频率为60.0%,而在对照组中为36.6%。长寿组中CC基因型的频率为51.0%,提示在长寿组和对照组中,也存在这种统计学意义。在百岁组和长寿组间,GNB3 825C/T的基因型和等位基因频率分布无统计学意义。进一步按照性别分组分析显示,该多态性不同基因型在长寿组与对照组男性及女性中的分布均无统计学差异。
结论
mtDNA5178A/C、10398G/A多态性与长寿相关,5178AA和10398GG基因型及A-G基因型组合(A-G单倍型)为长寿的保护因素。而5178CC及10398AA基因型则可能是影响长寿的不利因素。但在本项调查中,我们在mtDNA5178和10398位点分析的结果显示其基因型和等位基因频率未发现性别差异。GNB3基因825多态位点CC基因型与新疆和田地区维吾尔族人群寿命强相关,GNB3基因的C等位基因与该地区人群长寿呈显著正相关。
Backgroud
Aging is a universal biological reality that is familiar to everyone. The definition proposed by Robert Arking is one of the most global and rigorous descriptions of the aging process:“the time-independent series of cumulative, intrinsic, and deleterious functional and structural changes that usually begin to manifest themselves at reproductive maturity and eventually culminate in death.”If not, slow down the aging process, achieving old age.
Aging was attributed to development, genetic default, diseases and the inborn aging processing (IAP). In order to understand how to resist or delay the aging and attain the natural longevity human being owning, scientists proposed the various of mechanisms and theories, which involved oxidative stress, energy metabolism, signal transduction pathway, immune system and so on. Moreover, there were interaction among these mechanisms which affected by genetics. To identify the biological marker related to longevity was important to penetrate into the mechanisms that biomarkers-carriers escaped the common diseases and/or postponed the aging process. At present, the studies focused on genes related to inflammation and immune, insulin/ insulin-like growth factor (IGF-1) signaling pathway, genes related to lipid metabolism and oxidative stress, as well as mitochondrial genome.
The centenarian, who represents the extremity of longevity, was the optimal population of researching the human longevity. The quantity and relative ratio of centenarian in Xinjiang Hetian were over the average level of whole country, so Hetian was classified as one of four longevity regions in the world. Furthermore, because of environment, living characteristics, customs and habits, the Uygur who lived in this region became genetic isolation population and belonged to the natural longevity. Thereby, they were the value resource of genetic study about longevity.
Besides the common methods which compared the genotype distribution of single polymorphism between the longevities and the controls, the genetic methods of longevity study include the linkage disequilibrium and haplotype analysis, which became increasingly the effective methods of studying the life-span that was the complex phenotype controlled by multiple genes and gene-environment interaction. The linkage disequilibrium and haplotype analysis were valuable to association analysis, especially the association study of complex disease.
Objectives
To investigate the association between polymorphisms (5178A/C and 10398G/A) and their haplotype within mitochondrial DNA (mtDNA), as well as polymorphism 825 C/T of GNB3 gene and natural longevity in Xinjiang Uygur population.
Methods
We conducted a case-control study consisting of 165 natural longevity cases (including 65 centenarians and 100 people aged 90-99) and 112 area-, nationality-, gender-matched individuals who had no longevity family history and died in their 75 years were studied as control subjects. Their height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP), serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA) and blood glucose (BG) were measured. Genome DNA was extracted from white blood cells. Using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing technique, we tested the polymorphisms of 5178A/C and 10398G/A within mtDNA and 825C/T within GNB3 gene, and performed the linkage disequilibrium and haplotype analysis.
Results
The study about mtDNA polymorphisms showed the distribution frequency of the 5178A in the centenarian is slightly higher than in those of controls . The frequency of the 10398G were significantly higher among the centenarian and longevity in comparison to the controls. The frequency of AA genotype of 5178A/C polymorphism was higher obviously in the centenarian and longevity group than that in the control group, and the frequency of GG genotypes of 10398G/A polymorphism was higher obviously in the centenarian group than that in the control group. In 5178A/C and 10398G/A polymorphisms within mtDNA, there was no significant statistic difference of genotypes and allelics distribution between centenarian and longevity groups. There was no significantly statistic difference of distribution of every genotype between the same gender in the centenarian, longevity and control groups.
Analysis on 2-polymorphism combinations showed that the frequency of A-G genotypes combination of 5178/10398(A-G haplotype) was significantly higher in the centenarian and longevity groups than that in the controls.
In 825C/T polymorphisms within GNB3 gene, there was no significant difference of genotypes and allelics distribution between centenarian and longevity groups. The frequency of C/T polymorphism and alleles of the centenarians and longevity group were significantly different from that of the controls. The frequency rate of C/C genotype of the centenarians was significantly higher than of the controls . This significance also found between old-age groups and controls. No significant differences were found between centenarians and old–age groups for genotypes and allele frequency distribution. There was no significantly statistic difference of distribution of every genotype between the same gender in the centenarian, longevity and control groups.
Conclusions
AA genotype of 5178A/C polymorphism within mtDNA and GG genotype of 10398G/A polymorphism within mtDNA were the advantageous factor of longevity. However, CC genotype of 5178A/C polymorphism within mtDNA and AA genotype of 10398G/A polymorphism within mtDNA were the adverse factor of longevity. Furthermore, A-G genotypes combination(A-G haplotype) of 5178/10398 polymorphisms were the advantegeous factor of longevity, resulted from long-term genetic isolation in Uygur in Xinjiang Hetian.
There was correlation between the allelics and genotypes of polymorphisms within GNB3 gene 825C/T and natural longevity of Uygur population in Hetian. But no significant differences were found between centenarians and old–age groups for genotypes and allele frequency distribution. Our study suggest that GNB3 gene C825T polymorphism is closely correlated with life span of individuals in Xinjiang Hotan Uiygur population.
“健康与长寿”是生命科学永恒的主题,是21世纪人类最重要的奋斗目标和研究方向之一。那么,人为什么会衰老呢?衰老归因于发育、遗传失误、环境、疾病以及与生俱来的衰老进程(inborn aging process,IAP)。在衰老的研究中涉及对寿命的描述,其指标分为平均寿命和最大寿命。平均寿命决定人们对寿命的期望值。平均寿命与公共卫生状况和社会健康护理水平有关。最大寿命也就是寿命的极限,并不随公共卫生水平而改变。如何抵御或延缓衰老,达到人类应拥有的自然寿命,各国科学家从不同的角度提出了多种不同机制和理论,涉及到氧化应激、能量代谢、信号转导途径、免疫系统等多个系统的多种机制,而这些机制间又相互影响和作用,并在不同程度上受到遗传的影响。识别长寿相关生物学标记对深入理解其携带者免受常见疾病侵袭和/或衰老进程减慢的机制具有重要意义。目前,与炎症和免疫相关的基因、胰岛素/胰岛素样生长因子(insulin-like growth factor-1,IGF-1)信号途径、脂代谢相关基因以及氧化应激相关基因等成为研究热点,而线粒体基因组也逐渐成为研究的新方向。
百岁老人代表着寿命的极端情况,是进行人类长寿研究最佳的人群。新疆和田地区维吾尔族百岁老人数量和相对比例均高于全国平均水平,是世界四大长寿区之一。并且由于环境、生活特点及风俗习惯,形成了特殊的遗传隔离群,因此被称之为自然长寿人群,是长寿遗传学研究的难得资源。
长寿的遗传学研究方法,除常用的比较长寿者和对照人群之间单个多态性基因型分布的研究方法外,连锁不平衡和单倍型分析逐渐成为研究寿命这一受多基因及基因环境相互作用共同控制的复杂表型更为有效的遗传研究方法,对关联分析尤其复杂疾病的关联研究极为有用。
目的
探讨线粒体DNA(mitochondrial DNA,mtDNA)5178A/C、10398G/A多态性及其单倍型和G蛋白β3亚单位(G protein beta3 subunit,GNB3)基因C825T多态性与新疆和田地区维吾尔族自然长寿之间的关系。
方法
新疆和田地区275例研究对象均为和田地区常住居民,分为以下三组:165名年龄90岁以上的健康维吾尔族自然长寿个体分为百岁组(年龄≥100岁)65例,长寿组(年龄≥90岁、<100岁)100例,以112名地域、民族、性别相匹配的无长寿家族史,在75岁前自然死亡的个体为对照,进行流行病学调查。测定身高、体重、收缩压(systolic blood pressure,SBP)和舒张压(diastolic blood pressure,DBP)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、载脂蛋白A(apolipoprotein A,ApoA)和血糖(blood glucose,BG)水平。提取白细胞基因组DNA,分别采用PCR(polymerase chain reaction)、PCR-限制片段长度多态性(PCR-restriction fragment length polymorphism,PCR-RFLP)和PCR直接测序等技术对mtDNA 5178A/C、10398G/A多态性和GNB3基因C825T多态性进行基因分型,并进行单倍型分析。
结果
研究显示,mtDNA5178A/C和10398G/A多态性分析结果显示,百岁组和长寿组5178A等位基因和10398G等位基因频率较对照组明显增加。而百岁组和长寿组比较5178A等位基因和10398G等位基因频率分布无统计学意义。这与日本人群中的研究报告结果一致。我们同样发现,在百岁组5178AA与10398GG基因型组合明显高于对照组。我们认为线粒体DNA 5178AA及10398GG基因型与新疆和田地区维吾尔族自然长寿关联,而5178CC及10398AA基因型则可能是影响长寿的不利因素。单倍型分析显示每组有四种基因型组合,所有基因型组合频率分布在百岁组和长寿组中无统计学意义。然而,与对照组比较,百岁组和长寿组中mtDNA5178A/ 10398G基因型(A-G单倍型)组合明显高于对照组。细胞质基因多态性与长寿相关的诸多研究结果表明长寿与性别关联。但在本项调查中,我们对mtDNA5178A/C和10398G/A分析的结果显示其等位基因频率未发现性别差异。
对GNB3基因多态性的研究显示,在百岁组和对照组间,GNB3 825C/T的基因型和等位基因频率分布均具有统计学意义。其中在百岁组中CC基因型的频率为60.0%,而在对照组中为36.6%。长寿组中CC基因型的频率为51.0%,提示在长寿组和对照组中,也存在这种统计学意义。在百岁组和长寿组间,GNB3 825C/T的基因型和等位基因频率分布无统计学意义。进一步按照性别分组分析显示,该多态性不同基因型在长寿组与对照组男性及女性中的分布均无统计学差异。
结论
mtDNA5178A/C、10398G/A多态性与长寿相关,5178AA和10398GG基因型及A-G基因型组合(A-G单倍型)为长寿的保护因素。而5178CC及10398AA基因型则可能是影响长寿的不利因素。但在本项调查中,我们在mtDNA5178和10398位点分析的结果显示其基因型和等位基因频率未发现性别差异。GNB3基因825多态位点CC基因型与新疆和田地区维吾尔族人群寿命强相关,GNB3基因的C等位基因与该地区人群长寿呈显著正相关。
Backgroud
Aging is a universal biological reality that is familiar to everyone. The definition proposed by Robert Arking is one of the most global and rigorous descriptions of the aging process:“the time-independent series of cumulative, intrinsic, and deleterious functional and structural changes that usually begin to manifest themselves at reproductive maturity and eventually culminate in death.”If not, slow down the aging process, achieving old age.
Aging was attributed to development, genetic default, diseases and the inborn aging processing (IAP). In order to understand how to resist or delay the aging and attain the natural longevity human being owning, scientists proposed the various of mechanisms and theories, which involved oxidative stress, energy metabolism, signal transduction pathway, immune system and so on. Moreover, there were interaction among these mechanisms which affected by genetics. To identify the biological marker related to longevity was important to penetrate into the mechanisms that biomarkers-carriers escaped the common diseases and/or postponed the aging process. At present, the studies focused on genes related to inflammation and immune, insulin/ insulin-like growth factor (IGF-1) signaling pathway, genes related to lipid metabolism and oxidative stress, as well as mitochondrial genome.
The centenarian, who represents the extremity of longevity, was the optimal population of researching the human longevity. The quantity and relative ratio of centenarian in Xinjiang Hetian were over the average level of whole country, so Hetian was classified as one of four longevity regions in the world. Furthermore, because of environment, living characteristics, customs and habits, the Uygur who lived in this region became genetic isolation population and belonged to the natural longevity. Thereby, they were the value resource of genetic study about longevity.
Besides the common methods which compared the genotype distribution of single polymorphism between the longevities and the controls, the genetic methods of longevity study include the linkage disequilibrium and haplotype analysis, which became increasingly the effective methods of studying the life-span that was the complex phenotype controlled by multiple genes and gene-environment interaction. The linkage disequilibrium and haplotype analysis were valuable to association analysis, especially the association study of complex disease.
Objectives
To investigate the association between polymorphisms (5178A/C and 10398G/A) and their haplotype within mitochondrial DNA (mtDNA), as well as polymorphism 825 C/T of GNB3 gene and natural longevity in Xinjiang Uygur population.
Methods
We conducted a case-control study consisting of 165 natural longevity cases (including 65 centenarians and 100 people aged 90-99) and 112 area-, nationality-, gender-matched individuals who had no longevity family history and died in their 75 years were studied as control subjects. Their height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP), serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA) and blood glucose (BG) were measured. Genome DNA was extracted from white blood cells. Using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing technique, we tested the polymorphisms of 5178A/C and 10398G/A within mtDNA and 825C/T within GNB3 gene, and performed the linkage disequilibrium and haplotype analysis.
Results
The study about mtDNA polymorphisms showed the distribution frequency of the 5178A in the centenarian is slightly higher than in those of controls . The frequency of the 10398G were significantly higher among the centenarian and longevity in comparison to the controls. The frequency of AA genotype of 5178A/C polymorphism was higher obviously in the centenarian and longevity group than that in the control group, and the frequency of GG genotypes of 10398G/A polymorphism was higher obviously in the centenarian group than that in the control group. In 5178A/C and 10398G/A polymorphisms within mtDNA, there was no significant statistic difference of genotypes and allelics distribution between centenarian and longevity groups. There was no significantly statistic difference of distribution of every genotype between the same gender in the centenarian, longevity and control groups.
Analysis on 2-polymorphism combinations showed that the frequency of A-G genotypes combination of 5178/10398(A-G haplotype) was significantly higher in the centenarian and longevity groups than that in the controls.
In 825C/T polymorphisms within GNB3 gene, there was no significant difference of genotypes and allelics distribution between centenarian and longevity groups. The frequency of C/T polymorphism and alleles of the centenarians and longevity group were significantly different from that of the controls. The frequency rate of C/C genotype of the centenarians was significantly higher than of the controls . This significance also found between old-age groups and controls. No significant differences were found between centenarians and old–age groups for genotypes and allele frequency distribution. There was no significantly statistic difference of distribution of every genotype between the same gender in the centenarian, longevity and control groups.
Conclusions
AA genotype of 5178A/C polymorphism within mtDNA and GG genotype of 10398G/A polymorphism within mtDNA were the advantageous factor of longevity. However, CC genotype of 5178A/C polymorphism within mtDNA and AA genotype of 10398G/A polymorphism within mtDNA were the adverse factor of longevity. Furthermore, A-G genotypes combination(A-G haplotype) of 5178/10398 polymorphisms were the advantegeous factor of longevity, resulted from long-term genetic isolation in Uygur in Xinjiang Hetian.
There was correlation between the allelics and genotypes of polymorphisms within GNB3 gene 825C/T and natural longevity of Uygur population in Hetian. But no significant differences were found between centenarians and old–age groups for genotypes and allele frequency distribution. Our study suggest that GNB3 gene C825T polymorphism is closely correlated with life span of individuals in Xinjiang Hotan Uiygur population.
引文
[1]承鲁主编.当代生物学.北京:中国致公出版社. 2000, 394-396.
[2] Sinclair DA, Lin SJ, Guarente L. Life-span extension in yeast[J]. Science, 2006, 312:195-196.
[3] Harman D. Aging[J]. Ann N Y Acad Sci. 2001, 928:1-21.
[4] Alexeyev MF, Lecloux SP, Wilson GL. Mitochondrial DNA and aging[J]. Clinical Science. 2004, 107:355-364.
[5] Barja G. Free radicals and aging[J]. Trends Neurosci. 2004, 27 (10):595-600.
[6] Harman D. Free radical theory of aging:an update:increasing the functional life span[J]. Ann N Y Acad Sci. 2006, 1067:10-21.
[7] Gavrilova NS, Gavrilov LA. When Does Human Longevity Start?:Demarcation of the Boundaries for Human Longevity[J]. Journal of anti-aging medicine. 2001, 4(2):115-124.
[8] Olshansky SJ, Rattan SS. The biology of aging. Mount Sinai J Med, 2003, 70:3-22.
[9]赵增翰:概论.见:童坦君?张宗玉主编.医学老年学.北京:人民卫生出版社, 2006. 1-13.
[10] Frisard M, Ravussin E. Energy metabolism and oxidative stress-impact on the metabolic syndrome and the aging process. Endocrine, 2006, 29:27-32.
[11] Gavrilov LA, Gavrilova NS. Evolutionary theories of aging and longevity[J]. The Scientific World JOURNAL. 2002, 2:339-356.
[12] Parsons PA. Life span:does the limit to survival depend upon metabolic efficiency under stress[J]? Biogerontology. 2002, 3(4):233-41.
[13] Vermeulen CJ, Loeschcke V. Longevity and the stress response in Drosophila[J]. Exp Gerontol. 2007, 42(3):153-9.
[14] Terry DF, Wyszynski DF, Nolan VG, et al. Serum heat shock protein 70 level as a biomarker of exceptional longevity[J]. Mech Ageing Dev. 2006, 127(11):862-8.
[15] Singh R, Kolvraa S, Bross P, et al. Heat-shock protein 70 genes and human longevity:a view from Denmark[J]. Ann N Y Acad Sci. 2006, 1067:301-8.
[16] Colotti C, Cavallini G, Vitale RL, et al. Effects of aging and anti-aging caloric restrictions on carbonyl and heat shock protein levels and expression[J]. Biogerontology. 2005, 6(6):397-406.
[17] Sun J, Folk Donna, Bradley TJ, et al. Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span adult drosophila melangaster[J].Genetics. 2002, 161:661-672.
[18] Criscuolo F, Gonzalez-Barroso MM, Maho YL, et al. Avian uncoupling protein expressed in yeast mitochondria prevents endogenous free radical damage[J]. Proc R Soc B. 2005, 272:803-810.
[19] Salvioli S, Bonafe M, Capri M, et al. Mitochondria, aging and longevity—a new perspective[J]. Febs Lett. 2001, 492(1-2):9-13.
[20] Andziak B, Buffenstein R. Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice[J]. Aging Cell. 2006, 5(6):525-32.
[21] Ali SS, Xiong C, Lucero J, et al. Gender differences in free radical homeostasis during aging:shorter-lived female C57BL6 mice have increased oxidative stress[J]. Aging Cell. 2006, 5(6):565-74.
[22] Holliday R. Food, fertility and longevity[J]. Biogerontology. 2006, 7(3):139-141.
[23] Denny CA, Kasperzyk JL, Gorham KN, et al. Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice[J]. J Neurosci Res. 2006, 83(6):1028-38.
[24] Barros MH, Bandy B, Tahara EB, et al. High respiratory activity decreases mitondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae[J]. J Biol Chem. 2004, 279:49883-49888.
[25] Sreekumar R, Unnikrishnan J, Fu A, et al. Effects of caloric restriction on mitochondrial function and gene transcripts in rat muscle[J]. Am J Physiol Endocrinol Metab. 2002, 283:E38-E43.
[26] Willcox DC, Willcox BJ, Todoriki H, et al. Caloric restriction and human longevity:what can we learn from the Okinawans?[J]Biogerontology. 2006, 7(3):173-177.
[27] Wolf G. Calorie restriction increases life span:a molecular mechanism[J]. Nutr Rev. 2006, 64:89-92.
[28] Anderson RM, Weindruch R. Metabolic reprogramming in dietary restriction[J]. Interdiscip Top Gerontol. 2007, 35:18-38.
[29] Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging[J]. Science, 1996, 253(5271):59-63.
[30] Kua CH. Uncoupling the relationship between fatty acids and longevity[J]. IUBMB Life. 2006, 58(3):153-5.
[31] Lee K AJM, Willemsen PHM, Vusse GJ, et al. Effects of fatty acids on uncouplingprotein-2 expression in the rat heart[J]. FASEB J, 2002, 14(3):495-502.
[32] Wolkow CA, Iser WB. Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan[J]. Ageing Res Rev. 2006, 5(2):196-208.
[33] Sanz A, Gomez J, Caro P, et al. Carbohydrate restriction does not change mitochondrial free radical generation and oxidative DNA damage[J]. J Bioenerg Biomembr. 2006, 38(5-6):327-33.
[34] Sanz A, Gomez J, Caro P, et al. Effect of lipid restriction on mitochondrial free radical production and oxidative DNA damage[J]. Ann N Y Acad Sci. 2006, 1067:200-9.
[35] Ingram DK, Zhu M, Mamczarz J, et al. Calorie restriction mimetics:an emerging research field[J]. EAging Cell. 2006, 5(2):97-108.
[36] Andziak B, O'Connor TP, Qi W, et al. High oxidative damage levels in the longest-living rodent, the naked mole-rat.[J]Aging Cell. 2006, 5(6):463-71.
[37] Magwere T, West M, Riyahi K, et al. The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster[J]. Mech Ageing Dev. 2006, 127(4):356-70.
[38] Lehtinen MK, Yuan Z, Boag PR, et al. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span[J]. Cell. 2006, 125(5):987- 1001.
[39] Geminard C, Arquier N, Layalle S, et al. Control of metabolism and growth through insulin-like peptides in Drosophila[J]. Diabetes. 2006, 55 Suppl 2:S5-8.
[40] Baumeister R, Schaffitzel E, Hertweck M. Endocrine signaling in Caenorhabditis elegans controls stress response and longevity[J]. J Endocrinol. 2006, 190(2):191- 202.
[41] Thum T, Hoeber S, Froese S, et al. Age-Dependent Impairment of Endothelial Progenitor Cells is Corrected by Growth Hormone Mediated Increase of Insulin- Like Growth Factor-1[J]. Circ Res. 2007, 100:434.
[42] Murphy CT. The search for DAF-16/FOXO transcriptional targets:approaches and discoveries[J]. Exp Gerontol. 2006, 41(10):910-21.
[43] Murakami S. Stress resistance in long-lived mouse models[J]. Exp Gerontol. 2006, 41(10):1014-9.
[44] Wang Y, Oh SW, Deplancke B, et al. C. elegans 14-3-3 proteins regulate life span and interact with SIR-2. 1 and DAF-16/FOXO[J]. Mech Ageing Dev. 2006, 127(9):741-7.
[45] Berdichevsky A, Viswanathan M, Horvitz HR, et al. C. elegans SIR-2. 1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span[J]. Cell. 2006, 125(6):1165-77.
[46] Curtis R, O'Connor G, DiStefano PS. Aging Cell. Aging networks in Caenorhabditis elegans:AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways[J]. 2006, 5(2):119-26.
[47] Wolff S, Ma H, Burch D, et al. SMK-1, an essential regulator of DAF-16-mediated longevity.[J]Cell. 2006, 124(5):1039-53.
[48] Troemel ER, Chu SW, Reinke V, et al. p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans[J]. PLoS Genet. 2006, 2(11):e183.
[49] Candore G, Colonna-Romano G, Balistreri CR, et al. Biology of longevity:role of the innate immune system[J]. Rejuvenation Res. 2006, 9(1):143-8.
[50] Delarosa O, Pawelec G, Peralbo E, et al. Immunological biomarkers of ageing in man:changes in both innate and adaptive immunity are associated with health and longevity[J]. Biogerontology. 2006, 7(5-6):471-81.
[51] Pawelec G. Immunity and ageing in man[J]. Exp Gerontol. 2006, 41(12):1239-42.
[52] Solana R, Pawelec G, Tarazona R. Aging and innate immunity[J]. Immunity. 2006, 24(5):491-4.
[53] Messaoudi I, Warner J, Fischer M, et al. Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates[J]. Proc Natl Acad Sci U S A. 2006, 103 (51):19448-53.
[54] Franceschi C, Capri M, Monti D, et al. Inflammaging and anti-inflammaging:A systemic perspective on aging and longevity emerged from studies in humans[J]. Mech Ageing Dev. 2007, 128 (1):92-105.
[55] Salvioli S, Capri M, Valensin S, et al. Inflamm-aging, cytokines and aging:state of the art, new hypotheses on the role of mitochondria and new perspectives from systems biology[J]. Curr Pharm Des. 2006, 12(24):3161-71.
[56] Vasto S, Candore G, Balistreri CR, et al. Mech Ageing Dev. Inflammatory networks in ageing, age-related diseases and longevity[J]. 2007, 128(1):83-91.
[57] Wieczorowska-Tobis K, Niemir ZI, Podkowka R, et al. Can an increased level of circulating IL-8 be a predictor of human longevity?[J]. Med Sci Monit. 2006, 12(3):CR118-21.
[58] Rontu R, Ojala P, Hervonen A, et al. Apolipoprotein E genotype is related to plasmalevels of C-reactive protein and lipids and to longevity in nonagenarians[J]. Clin Endocrinol (Oxf). 2006, 64(3):265-70.
[59] Scola L, Candore G, Colonna-Romano G, et al. Study of the association with -330T/G IL-2 in a population of centenarians from centre and south Italy[J]. Biogerontology. 2005, 6(6):425-9.
[60] Gavrilova NS, Gavrilov LA. The Reliability Theory of aging and longevity[J]J. theor. Biol. 2001, 213:527-545.
[61] Barzilaia N, Shuldinerb A. R. Searching for Human Longevity Genes:The Future History of Gerontology in the Post-genomic Era[J]. The Journals of Gerontology Series A:Biological Sciences and Medical Sciences. 2001, 56:M83-M87.
[62] Perls T, Terry D. Understanding the Determinants of Exceptional Longevity[J]. Annals of internal medicine. 2003, 139:445-449.
[63] Benedictis G. D, Tan QH, Jeune B. Recent advances in human gene–longevity association studies[J]. Mech Ageing Dev. 2001, 122(9):909-920.
[64] Pinkston JM, Garigan D, Hansen M, et al. Mutations that increase the life span of C. elegans inhibit tumor growth[J]. Science. 2006, 313(5789):971-5.
[65] Morrow G, Samson M, Michaud S, et al. Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress[J]. The FASEB Journal. 2004, 10. 1096fj. 03-0860fje.
[66] Puca AA, Daly MJ, Brewster SJ et al. A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4[J]. PNAS. 2001, 98(18):10505-10508.
[67] Capri M, Salvioli S, Sevini F, et al. The genetics of human longevity[J]. Ann N Y Acad Sci. 2006, 1067:252-63.
[68] Singh R, Kolvraa S, Bross P, et al. CReduced heat shock response in human mononuclear cells during aging and its association with polymorphisms in HSP70 genes[J]. ell Stress Chaperones. 2006, 11(3):208-15.
[69] Scola L, Lio D, Crivello A, et al. Analysis of HLA-DQA, HLA-DQB frequencies in a group of Sardinian centenarians[J]. Rejuvenation Res. 2006, 9 (1):157-60.
[70] Scriver CR, Beaudet AL, SLY WS, et al. The metabolic and molecular bases of inherited disease.[M]. 8th ed New York:Mc Graw–Hill Companies, 2001:2367-2509.
[71] Wallace DC. A mitochondrial paradigm for degenerative disease and aging[J]. Novartis Found Symp, 2001, 235:247-263.
[72] Wallace DC. A mitochondrial paradigm of metabolic and degenerative disease, aging and cancer:Adawn for evolutionary medicine[J]. Annu Rev Genet, 2005, 39:259-407.
[73]遆冬冬,张咸宁,等.人线粒体DNA与衰老和退行性疾病的研究进展.浙江大学学报(医学版). 2007, 36(1):93-97.
[74] Kivisild T, Tok HV, Park J, et al. The emerging limbs and twigs of the East Asian mtDNA tree[J]. Mol Biol Evol, 2002, 19(10):1737.
[75] Tanaka M, Gong J, Zhang J, et al. Mitochodrial genotype associated with longevity and its inhibitory effect on mutagenesis[J]. Mech Ageing Dev. 2000, 116(2-3):65-76.
[76] Wallace DC. The Human mitochondrial Sequence[EB/OL]. 2005-11-14. http://www. mitomap. org/mito seq html
[77] Brandon MC, Lott MT, Nguyen KC, et al. Mitomap:A Human mitochondrial genome database-2004 update[J]. NucleicAcidRes, 2005, 33(Database issue):D 611-D613.
[78] Byun DS, Venkatraman JT, Yu BP, et al. Modulation of antioxidant activities and immune response by food restriction in aging Ficher-344 rats[J]. Aging(Milano), 1995, 7:40-48.
[79] Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K. Mitochondrial genotype associatedwith longevity[J]. Lancet 1998;351:185-186.
[80] Holt IJ, Harding AE, Morgan-Hughes JA. Mitochondrial DNA deletion in mitochondrial myopathy[J]. Nature 1988;331:717-719.
[81] Howell N, Miller NR, Mackey DA, et al. Lightning Strikes Twice:Leber Hereditary Optic Neuropathy Families with Two Pathogenic mtDNA Mutations[J]. Neuro-Ophthalmology, 2002, 22(4):262-269.
[82] Tanaka M, Ino H, Ohno K, et al. Mitochondrial DNA mutations in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes(MELAS)[J]. Biochem Biophys Res Commun 1991;174:861-868.
[83] Linnane AW, Marzuki S, Ozawa T, Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative disease[J]. Lancet 1989, I, 642-645.
[84] Barja G, Herrero A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals[J]. The FASEB Journal. 2000, 14:312-318.
[85] Driver C, Georgiou A, Georgiou G. The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster[J]. Biogerontology. 2004, 5(3):185-92.
[86] Rebrin I, Sohal RS. Comparison of thiol redox state of mitochondria and homo- genates of various tissues between two strains of mice with different longevities[J]. Exp Gerontol. 2004, 39(10):1513-1519.
[87] Siffert, W(2003) G-protein beta 3 subunit 825T allele and hypertension. Curr Hypertens. Rep. , 5, 47-53.
[88] BenJafield, A. V. , Jeyasingam, C. L. , Nyholt, D. R. , Griffiths, L. R. & Morris, B. J. G-protein beta 3 subunit gene(GNB3) variant in Causation of essential hypertension. Hyper tension, 1998, 32, 1094-1097.
[89] Schunkert, H. , Hense, H. W. , Doring, A. , Riegger, G. A, & Siffert, W. Association between a polymorphism in the G protein beta 3 subunit gene and lower renin and elevated diastolic blood pressure levels. Hypertension, 1998, 32, 510-513.
[90] Siffert, W. , Rosskopf, D. , Siffert, G. , et al. Association of a human G-protein beta 3 subunit variant with hypertension. Nat. Genet, 1998, 18:45-48.
[91] Beige, J. , Hohenbleicher, H. , Distlar, A. & Sharma, A. M. (1999) G-Protein beta 3 subunit C825T variant and ambulatory blood pressure in essential hypertension. Hypertension, 33:1049-1051.
[92] Dong, Y. , Zha, H. , Sagnella, G, A. , Carter, N. D. , Cook, D. C. & Cappuccio, F. P. (1991) Association between the C825T polymorphism of the G protein beta 3-subunit gene and hypertension in blacks. Hypertension, 34, 1193-1196.
[93] Hengstanberg, C. , Schunkert, H. , Mayer, B. , Doring, A. , Lowel, H. , Hense, H. W. , Fischer, M. , Riegger, G. A, & Holmer, S. R (2001) Association between a polymorphism in the G protein beta 3 subunit gene(GNB3) with arterial hypertension but not with myocardial infarction. Cardiovasc, Res. , 49, 820-827.
[94] Gutersohn, A. , Naber, C. , Muller, N. , Erbel, R. & Siffert, W. , (2000) G protein beta 3 subunit 825TT genotype and post-pregnancy weight retention. Lancet, 355, 1240-1241.
[95] Brand, E. , Wang, J. G. , Hermann, S. M. & Staessen, J. A. (2003) An epidemiological study of blood pressure and metabolic phenotypes in relation to the G beta 3 C825T polymorphism. J. Hypertens. , 21, 729-737.
[96] Dishy. V. , Gupta S. , Landan, R. , Xie, H. G. , Kim, R. B. , Smiley, R. M. , Byrne, D. W. , Wood, A. J. & Stein, C. M. (2003) G-protein beta(3) Subunit 825C/Tpolymorphism is associated with weight gain during pregnancy. Pharmacogenetics, 13, 241-242.
[97] Terra, S. G. , Mcgorray, S. P. , Wu, R. , Mc Namara D, M. , Cavallari, L. H. , Walker, J. R. , Wallace, M. R. , Johnson, B. D. , Bairey Merz, C, N. , Sopko, G. , Pepine, C. J. & Johnson, J. A. (2005) Association betweenβ-adreneregic receptor polymorphisms and their G-protein-coupled receptors with body mass index and obesity in women:a report from the NHLBI-sponsored WISE Study. Int. J. Obesity. , 29, 746-754.
[98] Siffert W, Rorster P, Jockel KH et al. (1999) Worldwide ethnic distribution of the G-protein Beta-3 subunit 825T allele and its association with obesity in Caucasian, Chinese and Black African individuals. J Am Soc Nephrol. , 10(9):1921-1930.
[99] Neer, E. , Clapham, D. (1988) Roles of G protein subunits in transmembrane signaling. Nature. , 333, 129-134.
[100]Fuller, G. , Shield, S. D. (1998) Molecular basis of medical cell biology. Appleton & Lange, London. , 233-245.
[101]Rosskopf, D. , Busch, S. , Man they I et al(2000) G protein beta 3 gene:Structure, promoter and additional polymorphisms. Hypertension. , 1, 33-41.
[102]Greegorz, D. , PatrycJa, G. S. , Andrzej, P. , et al. (2002) G-proteinβ3 subunit gene C825T polymorphism is associated with arterial hypertension in Polish patients with type 2 diabetes mellitus, Med, Sci, Mouit, 8(8), CR597-602.
[103]Mitchell, A. , Luckebergfeld, B. , Bulumann, S. , et al. (2004) Effect of systemic endothelin A receptor antagonism in various vascular beds in men:in vivo interactions of the major blood pressure-regulating systems and association with the GNB3 polymorphism, Clin Pharmacol Ther, 76(6):396-408.
[104]Danoviz, M. , Pereira, A. , Mill, J. , et al. (2006) Hypertension, obesity and gnb3 gene variants, Clin Exp Pharmacol Physiol, 33(3):248-252.
[105]Ferrari, P. , Ferrandi, M. , Valentini, J. , et al. (2006) Rostafuroxin:an ouabain antagonist that corrects renal and vascular Na-K-ATPase alterations in ouabain and adducin-dependent hypertension, Am J Physiol Regul Integr Comp Physiol, 290(3):R529-535.
[106]Sartori, M. , Parotto, E. , Ceolotto, G. , et al. (2004) C825T polymorphism of the GNB3 gene codifying the G-protein beta-3 subunit and cardiovascular risk, Ann Ital Med Int, 19(4):240-248.
[107]Ogimoto, A. (2004) Polymorphism in guanine nucleotide-bin ding protein (G-protein) beta 3 subunit (GNB3) gene as a risk factor in the development ofhypertensive organ damage, Nippon Rinsho 62(Suppl 3):126-130.
[108]Von Beckerath, N. , Schusterschit, Z. Y. , Koch, W. , et al. (2003) G protein beta 3 subunit 825T allele carriage and risk of coronary artery disease, Atherosclerosis, 167(1):135-139.
[109]Kanai N, Fujii T, Saito K, et al, (1994) Rapid and simple method for preparation of genomic DNA from easily obtainable clotted blood. Clin Pathol, 47:1043-1044.
[110]Neer, E. L. (1995) Heterotrimeric G proteins:organizer of transwenbrane signals, Cell, 80:249-257.
[111]Hamm, A. E. The many faces of G protein signaling, J Biol Chem, 1998, 273:669-672.
[112]Siffert, W. , Rosskopf, D. , Moritz, A. (1995) Enhanced G protein activation in immortalized lymphoblasts from patients with essential hypertension. J Clin Invest, 96:759-766.
[113]Suwazono, Y. , Okubo, Y. , Kobayashi, E. , Miura, K. , Morikawa, Y. , Ishizaki, M. , Kido, T. , Nakagawa, H & Nogawa, K. (2004a) Lack of association between human G-protein beta 3 subunit variant and overweight in Japanese workers. Obes, Res. , 12, 4-8.
[114]Suwazono, Y. , Okubo, Y. , Kobayashi, E. , Miura, K. , Morikawa, Y. , Ishizaki, M. , Kido, T. , Nakagawa, H & Nogawa, K. (2004b) Lack of association of human G-protein beta 3 subunit variant with hypertension in Japanese Workers. J. Hypertens. , 22, 493-500.
[115]Buchmayer, H. , Sunder-Plassmann, G. , Hirschl, M. , et al(2000) G-protein beta 3 subunit gene (GNB3) polymorphism 805C/T in patients with hypertensive crisis. Critical Care Medicine, 9:3203-3206.
[116]Tsai, C. , Yeh, H. , Chon, Y. , et al(2000) G protein beta 3 subunit variant and essential hypertension in Taiwain;a case-control study. Int J of Cavdiol, 2:191-195.
[117]Poch, E. , Gonzales, D. , Gomez-Angelats, E. (2000) G-protein beta(3) subunit gene variant and left ventricular hypertrophy in essential hypertension, Hypertension, 1(part2):214-218.
[118]Von Beckerath, N. , Kastari, A. , Koch, W. , et al. (2000) G protein beta 3 subunit polymorphism and risk of thrombosis and restenosis following coronary stant placement, Athe- rosclerosis, 149(1):151-155.
[119]Siffert, W. , Forster, P. , Jockel, K. , Mvere, D. , et al(1999) World wide ethnic distribution of the G protein beta 3 subunit 825 T allele and its association withobesity in Caucasian, Chinese and Black African. J Amer Soc Nephrol, 9:1921-1930.
[120]Dalgaard LT, Pedersen O. Uncoupling proteins:functional characteristics and role in the pathogenesis of obesity and TypeⅡdiabetes[J]. Diabetologia. 2001, 44:946- 965.
[121]姜文锡,邱长春,程祖亨,等. ApoB基因3'端VNTR多态性与中国新疆维吾尔族自然长寿的比较研究[J].中华医学遗传学杂志. 2006 Oct;23(5):523-7.
[122]玛依拉·吾甫尔,方鸣武,程祖亨,等.载脂蛋白E基因多态性与新疆维吾尔族相关性研究[J].中华医学遗传学杂志. 2005, 22(4):462-463.
[123]Atzmon G, Rincon M, Schechter CB, et al. Lipoprotein genotype and conserved pathway for exceptional longevity in humans[J]. PLoS Biol. 2006, 4(4):562-569.
[124]Stakias N, Liakos P, Tsiapali E, et al. Lower prevalence of epsilon 4 allele of apolipoprotein e gene in healthy, longer-lived individuals of hellenic origin[J]. J Gerontol A Biol Sci Med Sci. 2006, 61 (12):1228-31.
[125]Seripa D, Franceschi M, Matera MG, et al. Sex differences in the association of apolipoprotein E and angiotensin-converting enzyme gene polymorphisms with healthy aging and longevity:a population-based study from Southern Italy[J]. J Gerontol A Biol Sci Med Sci. 2006, 61 (9):918-23.
[126]Edited by vital statistics governmental department of State Statistics Bureau. Annual report forms of China vital statistics[M]. Beijing:China statistics publishing company, 1993:52.
[127]Shifman S, Kuypers J, Kokoris M, et al. Linkage disequilibrium patterns of the human genome across populations[J]. Human Molecular Genetics. 2003, 12(7):771-776.
[128]Horne BD, Camp NJ. Principal component analysis for selection of optimal SNP sets that capture instragenicgenetic variation[J]. Genet Epidemiol. 2004, 26:11-21.
[129]何云刚,金力,黄薇.单核苷酸多态性与连锁不平衡研究进展基础医学与临床[J]. 2004, 24(5):487-490.
[130]Oberkofler H, Iglseder B, Klein K, et al. Associations of the UCP2 gene locus with asymptomatic carotid atherosclerosis in middle-aged women[J]. Arterioscler, Thromb, and Vasc Biol. 2005, 25:604-610.
[131]Dhamrait SS, Stephens J W, Cooper J A, et al. Cardiovascular risk in healthy men and markers of oxidative stress in diabetic men are associated with common variation in the gene for uncoupling protein 2[J]. European Heart Journal. 2004,25:468-475.
[132]陈晓燕,李山,秦雪.人类肿瘤中的线粒体DNA突变.应用预防医学, 2007,2: 57-59.
[133]Coskun PE, Pesini ER, Wallace DC. Control region mtDNA variants:longevity, climatic adaptation, and forensic conondrum[J]. Proc Natl Acad Sci USA, 2003, 100(6):2174.
[134]Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging[J]. Cell, 2005, 120(4):483-495.
[135]Chein KR, Karsent YG. Longevity and lineages:toward the integrative biology of degenerative diseases in heart, muscle, and bone[J]. Cell, 2005, 120(4):533-544.
[136]Feng CS, Ma HC, Yue Y, et al. Effect of propofol on the activation of nuclear factor kappaB and expression of imflammatory cytckines in ceveral cortex during transient focal ischemia in Parkinson:experiment in rats[J]. Zhonghua Yixue Zazhi, 2004, 84(24):2110.
[137]Trifunovi CA, Wredenberg A, Falkkenber GM, et al. Premature aging in mice expressing defective mitochondrial DNA polymerase[J]. Nature, 2004, 429(6990): 417-423.
[138]Kokaza A, Ishikawa M, Matsunaga N, et al. Longevity-associated mitochondrial DNA 5178A/C polymorphism and blood pressure in the Japanese population[J]. Hum Hypertens, 2004, 18:41-45. .
[139]Anderson S, Bankier AT, Barrell BG, et al. Sequence and organization of the human mitochondrial genome[J]. Nature, 1981, 290:457-465.
[140]Criscuolo F, Gonzalez-Barroso MM, Maho YL, et al. Avian uncoupling protein expressed in yeast mitichondria prevents endogenous free radical damage[J]. Proc R Soc B. 2005, 272:803-810.
[141]Driver C, Georgiou G. The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster[J]. Biogerontology, 2004, 5(3):185-92.
[142]Wolf G. Calorie restriction increase life span:a molecular mechanism[J]. Nutr Rev. 2006, 64:89-92.
[143]Ingram DK, Zhu M, Mamczarz J, te al. Calorie restriction mimetics:an emerging research field[J]. Aging Cell. 2006, 5(2):97-108.
[144]Navaro A, Gomes C, Lopez-Cepero MJ, te al. Beneficial effects of moderate exercise on mice aging:survival, behavior, oxdative stress, and mitochondrial electron transfer[J]. Am J Physiol Regul Integr Comp Physiol. 2004,286:R505-R511.
[145]Wallace D C. Mitochondrial genetics:a paradigm of metabolic and degenerative disease, aging, and cancer:A dawn for evolutionary medicine[J]. Annu Rev Genet, 2005, 39:259-407.
[146]De Benedictis G, Rose G, Carrieri G, et al. Mitochondrial DNA inharited variants are associated with successful aging and longevity in humans. FASEB J 1999;13:1532- 1536.
[147]Ivanova R, Lepage V, Charron D, Schachter F. Mitochondrial genotype associated with French Caucasian centenarians. Gerontology 1998;44:349.
[148]Ross OA, McCormack R, Curran MD, et al. Mitochondrial DNA polymorphism:its role in longevity of the Irish population. Exp Gerontol 2001;36:1161-1178.
[149]Niemi AK, Hervonen A, Hurme M, Karhunen PJ, Jylha M, Majiamaa K. Mitochondrial DNA polymorphisms associated with longevity in a Finnish population. Hum Genet 2003;112:29-33.
[150]Matsunaga H, Tanaka Y, Tanaka M, et al. Antiatherogenic mitochondrial genotype in patients with type 2 diabetes. Diabetes Care 2001;24:500-3.
[151]Kokaza A, Ishikawa M, Matsunaga N, et al. Association of the mitochondrialDNA 5178A/C polymorphism with serum lipid levels in the Japanese population. Hum Genet, 2001, 109(5):521
[152]Wang D, Taniyama M, Suzuki Y, et al. Association of the mitochondrial DNA 5178 A/C polymorphism with maternal inheritance and onset of type 2 diabetes in Japanese patients. Exp Clin Endocrinol Diabetes, 2001(109):361.
[153]Kokaza A, Ishikawa M, Matsunaga N, et al. Longevity-associated mitochondrialDNA 5178A/C polymorphism is associated with fasting plasma glocuse levels and glocuse tolerance in Japanese men. Mitochondrion, 2005, 5(6):418.
[154]Song XY, Lu B, Dong XH, et al. Association of the mitochondrial DNA 5178 A/C polymorphism with diabetic nephropathy in Chinese type 2 diabetic patients. Fudan Univ J Med Sci 2006, 33(4):479-482.
[155]Momiyama Y, Fuurutani M, Suzuki Y, et al. A mitichondrial DNA variant associated with left ventricular hypertrophy in diabetes. Biochem Biophys Res Commun, 2003, 312(3):858-864.
[156]Lenaz G, D’Aurelio M, Pich MM, et al. Mitochondrial bioenergetics in aging. Biochim Biophys Acta 2000;1459:397-404.
[157]Cann RL, Stoneking M, Wilson AC. Mitochondrial DNA and human evolution. Nature, 1987;325:31-36.
[158]Shimokata H, Yamada Y, Nakagawa M, et al. Distribution of genetic disease-related genotypes in the National Institute for Longevity Science, Longitudinal Study of Aging(NILS-LSA). J Epidemiol, 2000;10:S46-S55.
[159]Tanaka M. Mitochondrial genotypes and cytochromeb variants associated with longevity on Parkinson, s disease[J]. J Neurol, 2002, 249(supply 2):1111.
[160]Kato T, Kunugi H, Nanko S et al. Association of bipolar disorder with the 5178 polymorphism in mitochondrial DNA. Am J Med Gen 2000;96:182-186.
[161]Kato CH, Umekage T, Tochigi M et al. Mitochondrial DNA polymorphisms and extraversion. Am J Med Gen PartB 2004;128B:76-79.
[162]Holt IJ, Harding AE, Morgan-Hughes JA. Mitochondrial DNA deletion in mitochondrial myopathy[J]. Nature 1988;331:717-719.
[163]Howell N, Miller NR, Mackey DA, et al. Lightning Strikes Twice:Leber Hereditary Optic Neuropathy Families with Two Pathogenic mtDNA Mutations[J]. Neuro-Ophthalmology, 2002, 22(4):262-269.
[164]Linnane AW, Marzuki S, Ozawa T, Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative disease[J]. Lancet 1989, I, 642-645.
[165]Barja G, Herrero A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals[J]. The FASEB Journal. 2000, 14:312-318.
[166]Driver C, Georgiou A, Georgiou G. The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster[J]. Biogerontology. 2004, 5(3):185-92.
[167]Rebrin I, Sohal RS. Comparison of thiol redox state of mitochondria and homo- genates of various tissues between two strains of mice with different longevities[J]. Exp Gerontol. 2004, 39(10):1513-1519.
[168]Brunet-Rossinni AK. Reduced free-radical production and extreme longevity in the little brown bat (Myotis lucifugus) versus two non-flying mammals[J]. Mech Ageing Dev. 2004, 125 (1):11-20.
[169]Kovalenko SA, Tanaka M, Yoneda M, et al. Accumulation of somatic nucleotide substitutions in mitochondrial DNA associated with the 3243 A-to-G tRNA(leu)(UUR) mutation in encephalomyopathy and cardiomyopathy[J]. BiochemBiophys Res Commun 1996, 222:201-207.
[170]Lenaz G, D’Aurelio M, Pich MM, et al. Mitochondrial bioenergetics in aging. Biochim Biophys Acta 2000;1459:397-404.
[171]Qun Chen, Vazquez EJ, Moghaddas S, et al. Production of reactive oxygen species by mitochondria:central role of complexⅢ. J Biol Chem, 2003;278(38):36027.
[172]. Wallace D C. Mitochondrial genetics:a paradigm for aging and degenerative disease? Science 1992;256:628-632.
[173]Kang D, Hamasaki N. Alterations of mitochondrial DNA in common diaseses and diasese states:aging, neurodegeneration, heart failure, diabetes, and cancer. Curr Med Chem 2005;12(4):429-441.
[174]Kato T, Kunugi H, Nanko S et al. Mitochondrial DNA polymorphisms in bipolar disorder. J Affect Disord 2001;61:151-164.
[175]Cortopassi G A, Shibata D, Soong N W et al. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA 1992;89:7370-7374.
[176]Melov S, Shoffner J M, Kaufman A et al. Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle. Nuecleic Acids Res 1995;23:4122-4126.
[177]Kadenbach B, Muncher C, Frank V et al. human aging is associated with stochastic somatic mutations of mitochondrial DNA. Mutat Res 1995;338:161-172.
[178]Larson N G, Clayton D A. Molecular genetic aspects of human mitochondrial disorders. Annu Rev Genet 1995;29:151-178.
[179]Kamazawa A, Nishio Y, Kashiwagi A, et al. Reduced activity of mtDNA decrease the transcription in mitochondria isolated from diabetic rat heart. Am J Physiol Endocrinol Metab 2002;282(4);E778-85.
[180]Wallace D C. Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci USA 1994;91:8739-8746.
[181]Khan SM, Bennett JP Jr. Development of mitichondrial gene replacement therapy. J Bioenerg Biomembr, 2004;36(4):387-393.
[182]Wallace D C. Mitochondrial disease in man and mouse. Science 2000;283(5407):1482-1488.
[183]Michael R A, Richard G H. Mitochondrial influence on aging rate in Caenorhabditis elegans. Aging Cell 2004;3:29-34.
[184]Bartnik E, Lorenc A, Mroczek K. Human mitochondria in health, disease, aging andcancer. J Appl Genet 2001;42(1):65-71.
[185]Wei Y H, Lee H C. Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood) 2002, 227(9):671-682.
[186]De Grey A D. A proposed refinement of the mitochondrial free radical theory of aging. Bio Essays 1997;19:161-166.
[187]De Grey A D. The reductive hotspot hypothesis:un update. Arch Biochem Biophys 2000;373:295-301.
[188]Brunk U T, Terman A. The mitochondrial-lysosomal axis theory of aging:accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem 2002;269:1996-2002.
[189]Brand F N, Kiely D, Kannel W B et al. Family patterns of coronary heart disease mortality:the Framingham longevity study. J Epidemiol 1992;45:169-174.
[190]Giles R E, Blanc H, Cann H M et al. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci USA 1980;77:6715-6719.
[191]Borras C, Sastre J, Garcia-Sala D, et al. Mitochondria from females exhibit hiher antioxidant gene expression and lower oxidative damage than males[J]. Free Radic Biol Med, 200334;546-552?
[192]陈晶,潘尚领.线粒体DNA与衰老和长寿.现代医药卫生, 2006, 22(7):991-993.
[193]Niemi AK, Mailaren JS, Tanaka M, et al. Acombination of the common inherited mitochondrial DNA polymorphisms associated with longevity in a Finnish and Japanese subject[J]. Eur J Hum Genet 2005, 13(2):166
[194]Dato S, Passacino G, Rose G, et al. Association of the mitochondrial DNA haplogroup J with longevity is population specific[J]. Eur J Hum Genet 2004, 12(12):1080.
[195]Jazwinski SM. Aging and longevity genes. Acta Biochimica Polonica, 2000, 47(2):269-279.
[196]Rosskopf D, Busch S, Maanthey I, et al. G proteinβ3 gene:structure, promoter, and additional polymorphisms[J]. Hypertens, 2000,36:33-41.
[197]Levine MA, Smallwood PM, Moen PT, et al. Molecular cloning 0fβ3 subunit, a third form of the G proteinβ-subunit polypeptide[J]. Proc Natl Acad Sci USA. 1990;80:2329-2333.
[198]Clapham DE, Neer EJ. G proteinβγsubunits[J]. Annu Rev Pharmacol Toxicol, 1997, 37:167-203.
[199]Sondek J, Bohm A, Lambright DG, et al. Crystal structure of a GA proteinβγdimerat 2. 1 A resolution[J]. Nature, 1996;379:369-374.
[200]Levine MA, Smallwood PM, Moen PT, et al. Molecular cloning ofβ3 subunit, a third from of the Gproteinβ-subunit polypeptide[J]. Proc Natl Acad Sci USA, 1990, 80:2329-2333.
[201]Appel LJ, Champagne CM, Harsha DW, et al. Effects of the PREMIER clinical trial[J]. JAMA, 2003, 289(16):2083-2093.
[202]王淑英.高血压病的预防与健康教育新进展[J].医学综述, 2007, 13:432-434.
[203]王增武,武阳丰,赵连成,等.中国中年人群高血压患病率及知晓率?治疗率?控制率的演变趋势[J].中华流行病学杂志, 2004, 25(5):408.
[204]Beevers G, Lip JY, O, Brien E. ABC of human hypertension;the pathopysiology of hypertension[J]. BMJ, 2001, 322(7291):912-916.
[205]Izawa H, Yamada Y, Okada T, et al. Prediction of genetic risk for hypertension[J]. Hypertension, 2003, 41(3):1035-1040.
[206]Brand E, Hermann SM, Nicaud V, et al. The 825C-T polymorphism of the G protein subunit beta 3 is not related to hypertension[J]. Hypertension, 1999, 33(5):1175-1178.
[207]Hegele RA, Harris SB, Hanley AG, et al. G-protein beta 3 subunit variant and blood pressure variation in Canadian Oji-Gree[J]. Hypertens, 1998, 32:688-692.
[208]Schorr U, Blaschke K, Beige J, et al. G protein beta 3 subunit C825T allele and response to dietary salt in normotensive men[J]. J Hypertens, 2000, 18:855-859.
[209]Biao L, Dong LG, Yue LW, et al. G-protein beta 3 subunit gene variants and essential hypertension in the northen Chinese Han population[J]. Ann Hum Genet, 2005, 69:468-73.
[210]Huang X, Ju Z, Song Y, et al. Lack of association between G-protein beta 3 subunit gene and essential hypertension in Chinese:a case-control and a family-based study[J]. J Mol Med, 2003, 81:729-735.
[211]Bluthner K, Schmidt S, Siffert W, et al. increased frequency of G protein beta-3 subunit 825T allele in dialyzed patients with type diabetes[J]. Kidney Int, 1999, 55:1247-1250.
[212]Pietruck F, Spleiter S, Daul A, et al. Enhanced G protein activation in IDDM patients with diabetic nephropathy[J]. Diabetologia, 1998, 41:94-100.
[213]Viard P, Exner T, Maier U, et al. G betagamma dimers stimulate vascular L-type Ca2+ channels via phosphoinositide 3-kinase[J]. FAS EB J, 1999, 13(6):685-694.
[214]Jin J, Kunapuli SP. Coactivation of two different G protein–coupled receptors isessential for ADP-induced platelet aggregation[J]. Proc Natl Acad Sci USA, 1998, 95:8070-74.
[215]Von Beckerath, N. , Kastari, A. , Koch, W. , et al. G protein beta 3 subunit polymorphism and risk of thrombosis and restenosis following coronary stant placement[J]. Athe- rosclerosis, 2000, 149(1):151-155.
[216]Hengstenberg C, Schunkert H, Mayer B, et al. Association between a polymorphism in the G protein beta 3 subunit gene with arterial hypertension but not with myocardial infraction[J]. Cardiovasc Res, 2001, 49(4):820-827.
[217]Comuzzie AG, Allison DB. The search for human obesity genes[J]. Science, 1998, 280(5368):1374-1377.
[218]Poch E, Giner V, Gonzalez-Nunez D, et al. Association between a polymorphism in the G protein beta 3 subunit T allele with insulin resistance in essential hypertension[J]. Clin Exp Hypertens, 2002, 24(5):345-353.
[219]楼晓明,朱心强,秦建芬,等. GNB3基因C825T位点多态性与肥胖相关性[J].上海交通大学学报(医学版), 2006, 26(8):895- 898.
[220]Robert A, Anderson C, Young TK, et al. G protein beta 3 subunit gene splice variant and body fat distribution in Nunavut Inuit[J]. Genome Research, 1999, 9:972-977.
[221]Grzegorz D, Patrycja GS, Andrzej P, et al. G-protein beta 3 subunit gene C825T polymorphism is associatedwith arterial hypertension in Polish patients with type2 diabetes mellitus[J]. Med Sci Monit, 2002, 8(8):CR597-602.
[222]Strojek K, Grzeszczak W, Morawin E, et al. Nephropathy of typeII diabetis:Evidence for hereditary factors[J]?Kidney Int, 1997, 51:1602-1607.
[223]Fernandez RJ, Penarroja G, Richart C, et al. G protein beta-3 subunit 825T allele predicts improvement of insulin sensitivity and nitric oxide sensitivity in type2 diabetes mellitus[J]. Diabetes, 20001, 50(suppl 2):A289.
[224]Kiani JG, Saeed M, Parvez SH, et al. Association of G protein beta-3 subunit gene(GNB3) 825T allele with typeII diabetes[J]. Neuro Endocrinol Lett, 2005, 26(2):87-88.
[225]何燕,钟国强.原发性高血压后选基因的研究进展[J].医学综述, 2006, 12(18):1104-1106.
[226]Siffert, W, Rosskopf, D, Erbel R. Genetic polrmorphism of the G-protein beta 3 subunit, obesity and essential hypertension[J]. Herz, 2000, 25(1):26-33.
[227]王鸿懿,孙宁玲. GNB3基因多态性与心血管疾病[J].中国医师杂志, 2002增刊:383-385.
[1] Harman D. Aging[J]. Ann N Y Acad Sci. 2001, 928:1-21.
[2] Barja G. Free radicals and aging[J]. Trends Neurosci. 2004, 27(10):595-600.
[3] Criscuolo F, Gonzalez-Barroso MM, Maho YL, et al. Avian uncoupling protein expressed in yeast mitichondria prevents endogenous free radical damage[J]. Proc R Soc B. 2005, 272:803-810.
[4] Driver C, Georgiou G. The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster[J]. Biogerontology, 2004, 5(3):185-92.
[5] Wolf G. Calorie restriction increase life span:a molecular mechanism[J]. Nutr Rev. 2006, 64:89-92.
[6] Ingram DK, Zhu M, Mamczarz J, te al. Calorie restriction mimetics:an emerging research field[J]. Aging Cell. 2006, 5(2):97-108.
[7] Navaro A, Gomes C, Lopez-Cepero MJ, te al. Beneficial effects of moderate exercise on mice aging:survival, behavior, oxdative stress, and mitochondrial electron transfer[J]. Am J Physiol Regul Integr Comp Physiol. 2004, 286:R505-R511.
[8] Tanaka M, Gong JS, Zhang J, et al. Mitochondrial genotype associated with longevity and its inhibitory effect on mutagenesis. Mech[J]. Ageing Dev 2000;116:65-76.
[9] Anderson S, Bankier AT, Barrell, et al. Sequence and organization of the human mitochondrial genome[J]. Nature. 1981, 290:457-465.
[10] Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K. Mitochondrial genotype associated with longevity[J]. Lancet 1998;351:185-186.
[11] Holt IJ, Harding AE, Morgan-Hughes JA. Mitochondrial DNA deletion in mitochondrial myopathy[J]. Nature 1988;331:717-719.
[12] Howell N, Miller NR, Mackey DA, et al. Lightning Strikes Twice:Leber Hereditary Optic Neuropathy Families with Two Pathogenic mtDNA Mutations[J]. Neuro-Ophthalmology, 2002, 22(4):262-269.
[13] Tanaka M, Ino H, Ohno K, et al. Mitochondrial DNA mutations in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes(MELAS)[J]. Biochem Biophys Res Commun 1991;174:861-868.
[14] Linnane AW, Marzuki S, Ozawa T, Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative disease[J]. Lancet 1989, I,642-645.
[15] Barja G, Herrero A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals [J]. The FASEB Journal. 2000, 14:312-318.
[16] Driver C, Georgiou A, Georgiou G. The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster [J]. Biogerontology. 2004, 5(3):185-92.
[17] Rebrin I, Sohal RS. Comparison of thiol redox state of mitochondria and homo- genates of various tissues between two strains of mice with different longevities [J]. Exp Gerontol. 2004, 39(10):1513-1519.
[18] Brunet-Rossinni AK. Reduced free-radical production and extreme longevity in the little brown bat (Myotis lucifugus) versus two non-flying mammals [J]. Mech Ageing Dev. 2004, 125 (1):11-20.
[19] Kovalenko SA, Tanaka M, Yoneda M, et al. Accumulation of somatic nucleotide substitutions in mitochondrial DNA associated with the 3243 A-to-G tRNA(leu)(UUR) mutation in encephalomyopathy and cardiomyopathy[J]. Biochem Biophys Res Commun 1996, 222:201-207.
[20] Torroni A, Huoponen K, Francalacci p, tet al. Classification of European mtDNAs from analysis of three European populations[J]. Genetics 1996, 144:1835-1850.
[21] Van Den Bosch BJ, et al. Mutation analysis of the entire mitochondrial genome using denaturing high performance liquid chromatography[J]. Nucleic Acid Research, 2000, 28(20):E89.
[22]孙生,张惠芹,刘宗伟?当前线粒体DNA研究及在法医学中的应用[J].中国人民公安大学学报(自然科学版), 2006, 47:28-32.
[23] Gill P, Inavo PL, Kimpton C, et al. Identification of the remains of the Romanov family by DNA analysis[J]. Nat Genet, 1994, 6:130-135.
[24] Alexeyev MF, Lecloux SP, Wilson GL. Mitochondial DNA and aging[J]. Clinical Science. 2004, 107:355-364.
[25] Howell N, Kubacka I, Mackey DA. How rapidly does the human mitochondrial genome evolve[J]? Am J Hum Genet 1996, 59:501-9.
[26] Parsons TJ, Muniec DS, Sullivan K, et al. A high observed substitution rate in the human mitochondrial DNA control region[J]. Nat Gnet 1997, 15:363-8.
[27] Schon EA, Bonilla E, Dimaoru S. Mitochondrial DNA mutations and pathogenesis[J]. Bioenerg Biomembr 1997, 29:131-49.
[28] Dato S, Passarino G, Rose G, et al. Association of the mitochondrial DNA haplogroup J with longevity is population specific[J]. Eur J Hum Genet. 2004, 12(12):1080-2.
[29] Santoro A, Salvioli S, Raule N, et al. Mitochondrial DNA involvement in human longevity [J]. Biochim Biophys Acta. 2006, 1757(9-10):1388-99.
[30] Qun Chen, Vazquez EJ, Moghaddas S, et al. Production of reactive oxygen species by mitochondria:central role of complexⅢ. J Biol Chem, 2003;278(38):36027.
[31] Wallace D C. Mitochondrial genetics:a paradigm of metabolic and degenerative disease, aging, and cancer:A dawn for evolutionary medicine[J]. Annu Rev Genet, 2005, 39:259-407.
[32] Kang D, Hamasaki N. Alterations of mitochondrial DNA in common diaseses and diasese states:aging, neurodegeneration, heart failure, diabetes, and cancer. Curr Med Chem 2005;12(4):429-441.
[33] Jazwinski SM. Yeast longevity and aging-the mitochondrial connection [J]. Mech Ageing Dev. 2005, 126(2):243-248.
[34] Kato CH, Umekage T, Tochigi M et al. Mitochondrial DNA polymorphisms and extraversion[J]. Am J Med Gen PartB 2004;128B:76-79.
[35] Lack of correlation between mitochondrial reactive oxygen species production and life span in Drosophila[J]. Ann N Y Acad Sci. 2004, 1019:388-391.
[36] Corral-Debrinski M, Horton T, Lott MT, et al. Mitochondtial DNA deletions in human brain:regional variability and increase with advanced age[J]. Net Genet 1992, 2:324-9.
[37] Mashima Y, Kimura Y, Yamamoto Y, et al. Optic disc excavation in the atrophic stage of Leber, s hereditary optic neuropathy:comparison with normal tension glaucoma[J]. Greafes Arch Clin Exp Ophthalmol, 2003, 241:75-80.
[38]韦企平,孙艳红,宫晓红,等.中国人Leber遗传性视神经病变线粒体DNA突变的主要类型和临床特点[J].中华眼底病杂志, 2004, 20(2):78-80.
[39] Borras C, Sastre J, Garcia-Sala D, et al. Mitochondria from females exhibit hiher antioxidant gene expression and lower oxidative damage than males[J]. Free Radic Biol Med, 2003, 34;546-552.
[40] Carelli V. Leber, s hereditary optic neuropathy. In:Schapira AHV, DiMauro S. Mitochondrial Disorders in Neurology 2nd Edition. Boston:Butterworth-Heinemann, 2002, 115-142.
[41] Edland SD, Silverman JM, Peskind ER, et al. Increased risk of dementia in mothersof Alzheimer, s disease cases:evidence for maternal inheritance[J]. Neurology 1996, 47:254-6.
[42] Wooten GF, Currie LJ, Bennett JP, et al. Maternal inheritance in Parkenson, s disease[J]. Ann Neurol 1997, 41:265-8.
[43] Kosel S, Hofhaus G, Maassen A, et al. Role of mitochondrial in Parkenson, s disease[J]. Biol Chem, 1999, 380(7-8):865-870.
[44] Swerdlow RH, Parks JK, Cassarino DS, et al. Cybrids in Alzheimer, s disease:a cellular model of the disease[J]? Neurology 1997, 49:918-25.
[45] Hutchin T, Cortopassi GA. Mitochondrial DNA clone is associated with increased risk for Alzheimer, s disease [J]. Proc Natl Acad Sci USA, 1995, 92(15):6892-6895.
[46] Coskun PE, Ru Iz-pesin IE, Wallace DC. Control region mtDNA variats:longevity, climatic adaptation, and a forensic conundrum[J]. Proc Natl Acad Sci USA, 2003, 100(5):2174-2176.
[47] Hutchin TP, Heath PR, Pearson RC, et al. Mitochondrial DNA mutations in Alzheimer, s disease [J]. Biochim Biophys Res Commun 1997, 241:221-5.
[48] Cortopassi G A, Shibata D, Soong N W et al. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA 1992;89:7370-7374.
[49] Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging[J]. Cell 2005, 120(4):483-495.
[50] Chien KR, Karsenty G. Longevity and lineages:toward the integrative biology of degenerative diseases in heart, muscle, and bone[J]. Cell, 2005, 120(4):533-544.
[51] Davis RE, Miller S, Herrnstadt C, et al. Mutations in mitochondrial cytchrome c oxidase genes segregate with late-onset Alzheimer, s disease [J]. Proc Natl Acad Sci USA 1997, 94:4526-31.
[52] Pesce V, Connio A, Fracasso F. Age-related mitochondrial genotypic and phenotypic alterations in human skeletal muscle[J]. Free Radic Biol Med 2001, 30(11):607-17.
[53] Melov S, Shoffner J M, Kaufman A et al. Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle. Nuecleic Acids Res 1995;23:4122-4126.
[54] Hegele RA, Zinman B, Hanley AJG, et al. A commom mtDNA polymorphism associated with variation in plasma triglyceride concentration[J]. Am J Hum Genet 1997, 60:1552-5.
[55] Wallace D C. Mitochondrial disease in man and mouse. Science2000;283(5407):1482-1488.
[56] Michael R A, Richard G H. Mitochondrial influence on aging rate in Caenorhabditis elegans. Aging Cell 2004;3:29-34.
[57] Kato T, Kunugi H, Nanko S et al. Mitochondrial DNA polymorphisms in bipolar disorder. J Affect Disord 2001;61:151-164. Miwa S, Riyahi K, Partridge L, et al.
[58] Khan SM, Bennett JP Jr. Development of mitichondrial gene replacement therapy. J Bioenerg B, 2004;36(4):387-393.
[59] Wallace D C. The mitochondrial genome in human adaptive radiation and disease:on the road to therapeutics and performance enhancement[J]. Gene, 2005;354:169-180.
[60] Seo BB, Nakamaru-ogisu E, Cru ZP, et al. Functional expression of the single subunit NADH dehydrogenase in mitochondria in vivo:a potential therapy for complex I deficiencies[J]. Hum Gene Ther, 2004, 15(9):887-895.
[1] Appel LJ, Champagne CM, Harsha DW, et al. Effects of the PREMIER clinical trial[J]. JAMA, 2003, 289(16):2083-2093.
[2]王淑英.高血压病的预防与健康教育新进展[J].医学综述, 2007, 13:432-434.
[3]王增武,武阳丰,赵连成,等.中国中年人群高血压患病率及知晓率?治疗率?控制率的演变趋势[J].中华流行病学杂志, 2004, 25(5):408.
[4] Beevers G, Lip JY, O, Brien E. ABC of human hypertension;the pathopysiology of hypertension[J]. BMJ, 2001, 322(7291):912-916.
[5] Taroh liri, Bourne HR. G proteins propel surprise[J]. Nature Genetics, 1998, 18(1):8-10.
[6] Siffert, W. G-protein beta 3 subunit 825T allele and hypertension[J]. Curr Hypertens. Rep. 2003, 5:47-53.
[7] Rosskopf D, Busch S, Maanthey I, et al. G proteinβ3 gene:structure, promoter, and additional polymorphisms[J]. Hypertens, 2000, 36:33-41.
[8] Levine MA, Smallwood PM, Moen PT, et al. Molecular cloning 0fβ3 subunit, a third form of the G proteinβ-subunit polypeptide[J]. Proc Natl Acad Sci USA. 1990;80:2329-2333.
[9] Clapham DE, Neer EJ. G proteinβγsubunits[J]. Annu Rev Pharmacol Toxicol, 1997, 37:167-203.
[10] Sondek J, Bohm A, Lambright DG, et al. Crystal structure of a GA proteinβγdimer at 2. 1 A resolution[J]. Nature, 1996;379:369-374.
[11] Hamet P, Pausova Z, Adaricher V, et al. Hypertension:genes and environment[J]. J Hypertens, 1998, 16:397-418.
[12] Siffert, W. , Rosskopf, D. , Siffert, G. , Busch, S. , Moritz, A. , Erbel. R. , Sharma, A. M. , Rit2, E. , Wichmavn, H. E. , Jadobs, K. H. & Hors themke, B. Association of a human G-protein beta 3 subunit variant with hypertension[J]. Nat. Genet, 1998, 18:45-
[13] Beige J, Hohenbleicher H, Distler A, et al. G protein beta 3 subunit C825T variant and ambulatory blood pressure in essential hypertension[J]. Hypertension, 1999, 33(4):1049-1051.
[14] Adam VB, Chery LJ, Dale RN, et al. G-protein beta 3 subunit variant in Causation of essential hypertension[J]. Hypertens, 1998, 32:1094-97.
[15] Dong YB, Zhu HD, Sagnella GA, et al. Association between the C825Tpolymorphism of the G protein beta 3 subunit gene and hypertension in Blacks[J]. Hypertens, 1999, 34:1193-1196.
[16] Ogimoto, A. Polymorphism in guanine nucleotide-binding protein (G-protein) beta 3 subunit (GNB3) gene as a risk factor in the development of hypertensive organ damage[J]. Nippon Rinsho, 2004, 62(Suppl 3):126-130.
[17] Siffert, W. , Forster, P. , Jockel, K. , Mvere, D. , et al(1999) World wide ethnic distribution of the G protein beta 3 subunit 825 T allele and its association with obesity in Caucasian, Chinese and Black African. J Amer Soc Nephrol, 9:1921-1930.
[18] Izawa H, Yamada Y, Okada T, et al. Prediction of genetic risk for hypertension[J]. Hypertension, 2003, 41(3):1035-1040.
[19] Suwazono, Y. , Okubo, Y. , Kobayashi, E. , Miura, K. , Morikawa, Y. , Ishizaki, M. , Kido, T. , Nakagawa, H & Nogawa, K. Lack of association of human G-protein beta 3 subunit variant with hypertension in Japanese Workers[J]. J. Hypertens, (2004b), 22, 493-500.
[20] Tsai, C. , Yeh, H. , Chon, Y. , et al. G protein beta 3 subunit variant and essential hypertension in Taiwain;a case-control study[J]. Int J of Cavdiol, 2000, 2:191-195.
[21] Schorr U, Blaschke K, Beige J, et al. G protein beta 3 subunit C825T allele and response to dietary salt in normotensive men[J]. J Hypertens, 2000, 18:855-859.
[22] Mitchell, A. , Luckebergfeld, B. , Bulumann, S. , et al. Effect of systemic endothelin A receptor antagonism in various vascular beds in men:in vivo interactions of the major blood pressure-regulating systems and association with the GNB3 polymorphism[J]. Clin Pharmacol Ther, 2004, 76(6):396-408.
[23] Danoviz, M. , Pereira, A. , Mill, J. , et al. Hypertension, obesity and gnb3 gene variants[J]. Clin Exp Pharmacol Physiol, 2006, 33(3):248-252.
[24] Mahmood MS, Mian ZS, Afzal A, et al. G protein beta 3 subunit gene 825C>T dimorphism is associated with left ventricular hypertrophy but not essential hypertension[J]. Med Sci Monit, 2005, 11(1):CR6-CR9.
[25] Ferrari, P. , Ferrandi, M. , Valentini, J. , et al. Rostafuroxin:an ouabain antagonist that corrects renal and vascular Na-K-ATPase alterations in ouabain and adducin-dependent hypertension[J]. Am J Physiol Regul Integr Comp Physiol, 2006, 290(3):R529-535.
[26] Sartori, M. , Parotto, E. , Ceolotto, G. , et al. C825T polymorphism of the GNB3 gene codifying the G-protein beta-3 subunit and cardiovascular risk[J]. Ann Ital Med Int, 2004), 19(4):240-248.
[27]董会奕,李秋荣,王勤,等. ADD-1基因和GNB3基因多态性与原发性高血压相关性研究[J].岭南心血管病杂志, 2006, 12(4):258-261.
[28]李庆祥,李风衣,杜如跃,等.长裙地区原发性高血压与G蛋白β3亚单位基因C825T多态性[J].中国微循环杂志, 2006, 10(3):205-207.
[29]呼日勒,赵世刚,牛广明,等. G蛋白β3亚单位基因C825T多态性与蒙古族原发性高血压的相关性研究[J].中国优生与遗传杂志, 2006, 14(12):15-17.
[30] Tanira M, Balushi KL. Genetic variations related to hypertension:a review[J]. J Hum Hypertens, 2005, 19:7-19.
[31] Larson N, Hutchimson R, Boelwinkh E. Lack of association of 3 functional gerle variants with hypertension in African Americans[J]. Hypertension, 2000, 35(6):1297-1300.
[32] Budmmyer H, Sundar-Plassmann G, Hirsch, et al. G protein beta 3 subunit gene (GNB3) polymorphism 825C-T in patients with hypertensive crisis[J]. Crit Care Med, 2000, 28(9):203-206.
[33] Ishikawa K, Imai Y, Katsuya T, et al. Human G-protein beta 3 subunit variant is associated with potassium and total cholesterol levels but not with blood pressure[J]. Am Hypertens, 2000, 13(2):140-145.
[34] Brand E, Hermann SM, Nicaud V, et al. The 825C-T polymorphism of the G protein subunit beta 3 is not related to hypertension[J]. Hypertension, 1999, 33(5):1175-1178.
[35] Hegele RA, Harris SB, Hanley AG, et al. G-protein beta 3 subunit variant and blood pressure variation in Canadian Oji-Gree [J]. Hypertens, 1998, 32:688-692.
[36] Biao L, Dong LG, Yue LW, et al. G-protein beta 3 subunit gene variants and essential hypertension in the northen Chinese Han population[J]. Ann Hum Genet, 2005, 69:468-73.
[37] Huang X, Ju Z, Song Y, et al. Lack of association between G-protein beta 3 subunit gene and essential hypertension in Chinese:a case-control and a family-based study[J]. J Mol Med, 2003, 81:729-735.
[38] Neer, E. L. Heterotrimeric G proteins:organizer of transwenbrane signals[J]. Cell, 1995, 80:249-257.
[39] Kanai N, Fujii T, Saito K, et al. Rapid and simple method for preparation of genomic DNA from easily obtainable clotted blood[J]. Clin Pathol, 1994, 47:1043-1044.
[40] Hamm, A. E. (1998) The many faces of G protein signaling, J Biol Chem, 273:669-672.
[41] Siffert, W. , Rosskopf, D. , Moritz, A. (1995) Enhanced G protein activation in immortalized lymphoblasts from patients with essential hypertension. J Clin Invest, 96:759-766.
[42] Viard P, Exner T, Maier U, et al. G betagamma dimers stimulate vascular L-type Ca2+ channels via phosphoinositide 3-kinase[J]. FAS EB J, 1999, 13(6):685-694.
[43]何燕,钟国强.原发性高血压后选基因的研究进展[J].医学综述, 2006, 12(18):1104-1106.
[44] Siffert, W, Rosskopf, D, Erbel R. Genetic polrmorphism of the G-protein beta 3 subunit, obesity and essential hypertension [J]. Herz, 2000, 25(1):26-33.
[45]王鸿懿,孙宁玲. GNB3基因多态性与心血管疾病[J].中国医师杂志, 2002增刊:383-385.
[46] Jin J, Kunapuli SP. Coactivation of two different G protein–coupled receptors is essential for ADP-induced platelet aggregation[J]. Proc Natl Acad Sci USA, 1998, 95:8070-74.
[47] Von Beckerath, N, Schusterschit, ZY, Koch, W, et al. G protein beta 3 subunit 825T allele carriage and risk of coronary artery disease[J]. Atherosclerosis, 2003, 167(1):135-139.
[48] Von Beckerath, N. , Kastari, A. , Koch, W. , et al. G protein beta 3 subunit polymorphism and risk of thrombosis and restenosis following coronary stant placement[J]. Athe- rosclerosis, 2000, 149(1):151-155.
[49] Hengstenberg C, Schunkert H, Mayer B, et al. Association between a polymorphism in the G protein beta 3 subunit gene with arterial hypertension but not with myocardial infraction[J]. Cardiovasc Res, 2001, 49(4):820-827.
[50]张磊,董硷虎.肥胖体表测量指标与糖尿病及心血管病的研究进展[J].国外医学.内分泌学分册, 2005, 25(4):257-259.
[51] Cao H, Maeda K, Gorgun CZ, et al. Regulation of metabolic responses by adipocyte/macrophage Fatty Acid-binding proteins in leptin-deficient mice[J]. Diabetes, 2006, 55(4):257-259.
[52] Comuzzie AG, Allison DB. The search for human obesity genes[J]. Science, 1998, 280(5368):1374-1377.
[53] Poch E, Giner V, Gonzalez-Nunez D, et al. Association between a polymorphism in the G protein beta 3 subunit T allele with insulin resistance in essential hypertension[J]. Clin Exp Hypertens, 2002, 24(5):345-353.
[54]楼晓明,朱心强,秦建芬,等. GNB3基因C825T位点多态性与肥胖相关性[J].上海交通大学学报(医学版), 2006, 26(8):895- 898.
[55] Robert A, Anderson C, Young TK, et al. G protein beta 3 subunit gene splice variant and body fat distribution in Nunavut Inuit[J]. Genome Research, 1999, 9:972-977.
[56] Grzegorz D, Patrycja GS, Andrzej P, et al. G-protein beta 3 subunit gene C825T polymorphism is associatedwith arterial hypertension in Polish patients with type2 diabetes mellitus[J]. Med Sci Monit, 2002, 8(8):CR597-602.
[57] Strojek K, Grzeszczak W, Morawin E, et al. Nephropathy of typeII diabetis:Evidence for hereditary factors[J]?Kidney Int, 1997, 51:1602-1607.
[58] Bluthner K, Schmidt S, Siffert W, et al. increased frequency of G protein beta-3 subunit 825T allele in dialyzed patients with type diabetes[J]. Kidney Int, 1999, 55:1247-1250.
[59] Pietruck F, Spleiter S, Daul A, et al. Enhanced G protein activation in IDDM patients with diabetic nephropathy[J]. Diabetologia, 1998, 41:94-100.
[60] Fernandez RJ, Penarroja G, Richart C, et al. G protein beta-3 subunit 825T allele predicts improvement of insulin sensitivity and nitric oxide sensitivity in type2 diabetes mellitus[J]. Diabetes, 20001, 50(suppl 2):A289.
[61] Kiani JG, Saeed M, Parvez SH, et al. Association of G protein beta-3 subunit gene(GNB3) 825T allele with typeII diabetes[J]. Neuro Endocrinol Lett, 2005, 26(2):87-88.
[2] Sinclair DA, Lin SJ, Guarente L. Life-span extension in yeast[J]. Science, 2006, 312:195-196.
[3] Harman D. Aging[J]. Ann N Y Acad Sci. 2001, 928:1-21.
[4] Alexeyev MF, Lecloux SP, Wilson GL. Mitochondrial DNA and aging[J]. Clinical Science. 2004, 107:355-364.
[5] Barja G. Free radicals and aging[J]. Trends Neurosci. 2004, 27 (10):595-600.
[6] Harman D. Free radical theory of aging:an update:increasing the functional life span[J]. Ann N Y Acad Sci. 2006, 1067:10-21.
[7] Gavrilova NS, Gavrilov LA. When Does Human Longevity Start?:Demarcation of the Boundaries for Human Longevity[J]. Journal of anti-aging medicine. 2001, 4(2):115-124.
[8] Olshansky SJ, Rattan SS. The biology of aging. Mount Sinai J Med, 2003, 70:3-22.
[9]赵增翰:概论.见:童坦君?张宗玉主编.医学老年学.北京:人民卫生出版社, 2006. 1-13.
[10] Frisard M, Ravussin E. Energy metabolism and oxidative stress-impact on the metabolic syndrome and the aging process. Endocrine, 2006, 29:27-32.
[11] Gavrilov LA, Gavrilova NS. Evolutionary theories of aging and longevity[J]. The Scientific World JOURNAL. 2002, 2:339-356.
[12] Parsons PA. Life span:does the limit to survival depend upon metabolic efficiency under stress[J]? Biogerontology. 2002, 3(4):233-41.
[13] Vermeulen CJ, Loeschcke V. Longevity and the stress response in Drosophila[J]. Exp Gerontol. 2007, 42(3):153-9.
[14] Terry DF, Wyszynski DF, Nolan VG, et al. Serum heat shock protein 70 level as a biomarker of exceptional longevity[J]. Mech Ageing Dev. 2006, 127(11):862-8.
[15] Singh R, Kolvraa S, Bross P, et al. Heat-shock protein 70 genes and human longevity:a view from Denmark[J]. Ann N Y Acad Sci. 2006, 1067:301-8.
[16] Colotti C, Cavallini G, Vitale RL, et al. Effects of aging and anti-aging caloric restrictions on carbonyl and heat shock protein levels and expression[J]. Biogerontology. 2005, 6(6):397-406.
[17] Sun J, Folk Donna, Bradley TJ, et al. Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span adult drosophila melangaster[J].Genetics. 2002, 161:661-672.
[18] Criscuolo F, Gonzalez-Barroso MM, Maho YL, et al. Avian uncoupling protein expressed in yeast mitochondria prevents endogenous free radical damage[J]. Proc R Soc B. 2005, 272:803-810.
[19] Salvioli S, Bonafe M, Capri M, et al. Mitochondria, aging and longevity—a new perspective[J]. Febs Lett. 2001, 492(1-2):9-13.
[20] Andziak B, Buffenstein R. Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice[J]. Aging Cell. 2006, 5(6):525-32.
[21] Ali SS, Xiong C, Lucero J, et al. Gender differences in free radical homeostasis during aging:shorter-lived female C57BL6 mice have increased oxidative stress[J]. Aging Cell. 2006, 5(6):565-74.
[22] Holliday R. Food, fertility and longevity[J]. Biogerontology. 2006, 7(3):139-141.
[23] Denny CA, Kasperzyk JL, Gorham KN, et al. Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice[J]. J Neurosci Res. 2006, 83(6):1028-38.
[24] Barros MH, Bandy B, Tahara EB, et al. High respiratory activity decreases mitondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae[J]. J Biol Chem. 2004, 279:49883-49888.
[25] Sreekumar R, Unnikrishnan J, Fu A, et al. Effects of caloric restriction on mitochondrial function and gene transcripts in rat muscle[J]. Am J Physiol Endocrinol Metab. 2002, 283:E38-E43.
[26] Willcox DC, Willcox BJ, Todoriki H, et al. Caloric restriction and human longevity:what can we learn from the Okinawans?[J]Biogerontology. 2006, 7(3):173-177.
[27] Wolf G. Calorie restriction increases life span:a molecular mechanism[J]. Nutr Rev. 2006, 64:89-92.
[28] Anderson RM, Weindruch R. Metabolic reprogramming in dietary restriction[J]. Interdiscip Top Gerontol. 2007, 35:18-38.
[29] Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging[J]. Science, 1996, 253(5271):59-63.
[30] Kua CH. Uncoupling the relationship between fatty acids and longevity[J]. IUBMB Life. 2006, 58(3):153-5.
[31] Lee K AJM, Willemsen PHM, Vusse GJ, et al. Effects of fatty acids on uncouplingprotein-2 expression in the rat heart[J]. FASEB J, 2002, 14(3):495-502.
[32] Wolkow CA, Iser WB. Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan[J]. Ageing Res Rev. 2006, 5(2):196-208.
[33] Sanz A, Gomez J, Caro P, et al. Carbohydrate restriction does not change mitochondrial free radical generation and oxidative DNA damage[J]. J Bioenerg Biomembr. 2006, 38(5-6):327-33.
[34] Sanz A, Gomez J, Caro P, et al. Effect of lipid restriction on mitochondrial free radical production and oxidative DNA damage[J]. Ann N Y Acad Sci. 2006, 1067:200-9.
[35] Ingram DK, Zhu M, Mamczarz J, et al. Calorie restriction mimetics:an emerging research field[J]. EAging Cell. 2006, 5(2):97-108.
[36] Andziak B, O'Connor TP, Qi W, et al. High oxidative damage levels in the longest-living rodent, the naked mole-rat.[J]Aging Cell. 2006, 5(6):463-71.
[37] Magwere T, West M, Riyahi K, et al. The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster[J]. Mech Ageing Dev. 2006, 127(4):356-70.
[38] Lehtinen MK, Yuan Z, Boag PR, et al. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span[J]. Cell. 2006, 125(5):987- 1001.
[39] Geminard C, Arquier N, Layalle S, et al. Control of metabolism and growth through insulin-like peptides in Drosophila[J]. Diabetes. 2006, 55 Suppl 2:S5-8.
[40] Baumeister R, Schaffitzel E, Hertweck M. Endocrine signaling in Caenorhabditis elegans controls stress response and longevity[J]. J Endocrinol. 2006, 190(2):191- 202.
[41] Thum T, Hoeber S, Froese S, et al. Age-Dependent Impairment of Endothelial Progenitor Cells is Corrected by Growth Hormone Mediated Increase of Insulin- Like Growth Factor-1[J]. Circ Res. 2007, 100:434.
[42] Murphy CT. The search for DAF-16/FOXO transcriptional targets:approaches and discoveries[J]. Exp Gerontol. 2006, 41(10):910-21.
[43] Murakami S. Stress resistance in long-lived mouse models[J]. Exp Gerontol. 2006, 41(10):1014-9.
[44] Wang Y, Oh SW, Deplancke B, et al. C. elegans 14-3-3 proteins regulate life span and interact with SIR-2. 1 and DAF-16/FOXO[J]. Mech Ageing Dev. 2006, 127(9):741-7.
[45] Berdichevsky A, Viswanathan M, Horvitz HR, et al. C. elegans SIR-2. 1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span[J]. Cell. 2006, 125(6):1165-77.
[46] Curtis R, O'Connor G, DiStefano PS. Aging Cell. Aging networks in Caenorhabditis elegans:AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways[J]. 2006, 5(2):119-26.
[47] Wolff S, Ma H, Burch D, et al. SMK-1, an essential regulator of DAF-16-mediated longevity.[J]Cell. 2006, 124(5):1039-53.
[48] Troemel ER, Chu SW, Reinke V, et al. p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans[J]. PLoS Genet. 2006, 2(11):e183.
[49] Candore G, Colonna-Romano G, Balistreri CR, et al. Biology of longevity:role of the innate immune system[J]. Rejuvenation Res. 2006, 9(1):143-8.
[50] Delarosa O, Pawelec G, Peralbo E, et al. Immunological biomarkers of ageing in man:changes in both innate and adaptive immunity are associated with health and longevity[J]. Biogerontology. 2006, 7(5-6):471-81.
[51] Pawelec G. Immunity and ageing in man[J]. Exp Gerontol. 2006, 41(12):1239-42.
[52] Solana R, Pawelec G, Tarazona R. Aging and innate immunity[J]. Immunity. 2006, 24(5):491-4.
[53] Messaoudi I, Warner J, Fischer M, et al. Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates[J]. Proc Natl Acad Sci U S A. 2006, 103 (51):19448-53.
[54] Franceschi C, Capri M, Monti D, et al. Inflammaging and anti-inflammaging:A systemic perspective on aging and longevity emerged from studies in humans[J]. Mech Ageing Dev. 2007, 128 (1):92-105.
[55] Salvioli S, Capri M, Valensin S, et al. Inflamm-aging, cytokines and aging:state of the art, new hypotheses on the role of mitochondria and new perspectives from systems biology[J]. Curr Pharm Des. 2006, 12(24):3161-71.
[56] Vasto S, Candore G, Balistreri CR, et al. Mech Ageing Dev. Inflammatory networks in ageing, age-related diseases and longevity[J]. 2007, 128(1):83-91.
[57] Wieczorowska-Tobis K, Niemir ZI, Podkowka R, et al. Can an increased level of circulating IL-8 be a predictor of human longevity?[J]. Med Sci Monit. 2006, 12(3):CR118-21.
[58] Rontu R, Ojala P, Hervonen A, et al. Apolipoprotein E genotype is related to plasmalevels of C-reactive protein and lipids and to longevity in nonagenarians[J]. Clin Endocrinol (Oxf). 2006, 64(3):265-70.
[59] Scola L, Candore G, Colonna-Romano G, et al. Study of the association with -330T/G IL-2 in a population of centenarians from centre and south Italy[J]. Biogerontology. 2005, 6(6):425-9.
[60] Gavrilova NS, Gavrilov LA. The Reliability Theory of aging and longevity[J]J. theor. Biol. 2001, 213:527-545.
[61] Barzilaia N, Shuldinerb A. R. Searching for Human Longevity Genes:The Future History of Gerontology in the Post-genomic Era[J]. The Journals of Gerontology Series A:Biological Sciences and Medical Sciences. 2001, 56:M83-M87.
[62] Perls T, Terry D. Understanding the Determinants of Exceptional Longevity[J]. Annals of internal medicine. 2003, 139:445-449.
[63] Benedictis G. D, Tan QH, Jeune B. Recent advances in human gene–longevity association studies[J]. Mech Ageing Dev. 2001, 122(9):909-920.
[64] Pinkston JM, Garigan D, Hansen M, et al. Mutations that increase the life span of C. elegans inhibit tumor growth[J]. Science. 2006, 313(5789):971-5.
[65] Morrow G, Samson M, Michaud S, et al. Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress[J]. The FASEB Journal. 2004, 10. 1096fj. 03-0860fje.
[66] Puca AA, Daly MJ, Brewster SJ et al. A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4[J]. PNAS. 2001, 98(18):10505-10508.
[67] Capri M, Salvioli S, Sevini F, et al. The genetics of human longevity[J]. Ann N Y Acad Sci. 2006, 1067:252-63.
[68] Singh R, Kolvraa S, Bross P, et al. CReduced heat shock response in human mononuclear cells during aging and its association with polymorphisms in HSP70 genes[J]. ell Stress Chaperones. 2006, 11(3):208-15.
[69] Scola L, Lio D, Crivello A, et al. Analysis of HLA-DQA, HLA-DQB frequencies in a group of Sardinian centenarians[J]. Rejuvenation Res. 2006, 9 (1):157-60.
[70] Scriver CR, Beaudet AL, SLY WS, et al. The metabolic and molecular bases of inherited disease.[M]. 8th ed New York:Mc Graw–Hill Companies, 2001:2367-2509.
[71] Wallace DC. A mitochondrial paradigm for degenerative disease and aging[J]. Novartis Found Symp, 2001, 235:247-263.
[72] Wallace DC. A mitochondrial paradigm of metabolic and degenerative disease, aging and cancer:Adawn for evolutionary medicine[J]. Annu Rev Genet, 2005, 39:259-407.
[73]遆冬冬,张咸宁,等.人线粒体DNA与衰老和退行性疾病的研究进展.浙江大学学报(医学版). 2007, 36(1):93-97.
[74] Kivisild T, Tok HV, Park J, et al. The emerging limbs and twigs of the East Asian mtDNA tree[J]. Mol Biol Evol, 2002, 19(10):1737.
[75] Tanaka M, Gong J, Zhang J, et al. Mitochodrial genotype associated with longevity and its inhibitory effect on mutagenesis[J]. Mech Ageing Dev. 2000, 116(2-3):65-76.
[76] Wallace DC. The Human mitochondrial Sequence[EB/OL]. 2005-11-14. http://www. mitomap. org/mito seq html
[77] Brandon MC, Lott MT, Nguyen KC, et al. Mitomap:A Human mitochondrial genome database-2004 update[J]. NucleicAcidRes, 2005, 33(Database issue):D 611-D613.
[78] Byun DS, Venkatraman JT, Yu BP, et al. Modulation of antioxidant activities and immune response by food restriction in aging Ficher-344 rats[J]. Aging(Milano), 1995, 7:40-48.
[79] Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K. Mitochondrial genotype associatedwith longevity[J]. Lancet 1998;351:185-186.
[80] Holt IJ, Harding AE, Morgan-Hughes JA. Mitochondrial DNA deletion in mitochondrial myopathy[J]. Nature 1988;331:717-719.
[81] Howell N, Miller NR, Mackey DA, et al. Lightning Strikes Twice:Leber Hereditary Optic Neuropathy Families with Two Pathogenic mtDNA Mutations[J]. Neuro-Ophthalmology, 2002, 22(4):262-269.
[82] Tanaka M, Ino H, Ohno K, et al. Mitochondrial DNA mutations in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes(MELAS)[J]. Biochem Biophys Res Commun 1991;174:861-868.
[83] Linnane AW, Marzuki S, Ozawa T, Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative disease[J]. Lancet 1989, I, 642-645.
[84] Barja G, Herrero A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals[J]. The FASEB Journal. 2000, 14:312-318.
[85] Driver C, Georgiou A, Georgiou G. The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster[J]. Biogerontology. 2004, 5(3):185-92.
[86] Rebrin I, Sohal RS. Comparison of thiol redox state of mitochondria and homo- genates of various tissues between two strains of mice with different longevities[J]. Exp Gerontol. 2004, 39(10):1513-1519.
[87] Siffert, W(2003) G-protein beta 3 subunit 825T allele and hypertension. Curr Hypertens. Rep. , 5, 47-53.
[88] BenJafield, A. V. , Jeyasingam, C. L. , Nyholt, D. R. , Griffiths, L. R. & Morris, B. J. G-protein beta 3 subunit gene(GNB3) variant in Causation of essential hypertension. Hyper tension, 1998, 32, 1094-1097.
[89] Schunkert, H. , Hense, H. W. , Doring, A. , Riegger, G. A, & Siffert, W. Association between a polymorphism in the G protein beta 3 subunit gene and lower renin and elevated diastolic blood pressure levels. Hypertension, 1998, 32, 510-513.
[90] Siffert, W. , Rosskopf, D. , Siffert, G. , et al. Association of a human G-protein beta 3 subunit variant with hypertension. Nat. Genet, 1998, 18:45-48.
[91] Beige, J. , Hohenbleicher, H. , Distlar, A. & Sharma, A. M. (1999) G-Protein beta 3 subunit C825T variant and ambulatory blood pressure in essential hypertension. Hypertension, 33:1049-1051.
[92] Dong, Y. , Zha, H. , Sagnella, G, A. , Carter, N. D. , Cook, D. C. & Cappuccio, F. P. (1991) Association between the C825T polymorphism of the G protein beta 3-subunit gene and hypertension in blacks. Hypertension, 34, 1193-1196.
[93] Hengstanberg, C. , Schunkert, H. , Mayer, B. , Doring, A. , Lowel, H. , Hense, H. W. , Fischer, M. , Riegger, G. A, & Holmer, S. R (2001) Association between a polymorphism in the G protein beta 3 subunit gene(GNB3) with arterial hypertension but not with myocardial infarction. Cardiovasc, Res. , 49, 820-827.
[94] Gutersohn, A. , Naber, C. , Muller, N. , Erbel, R. & Siffert, W. , (2000) G protein beta 3 subunit 825TT genotype and post-pregnancy weight retention. Lancet, 355, 1240-1241.
[95] Brand, E. , Wang, J. G. , Hermann, S. M. & Staessen, J. A. (2003) An epidemiological study of blood pressure and metabolic phenotypes in relation to the G beta 3 C825T polymorphism. J. Hypertens. , 21, 729-737.
[96] Dishy. V. , Gupta S. , Landan, R. , Xie, H. G. , Kim, R. B. , Smiley, R. M. , Byrne, D. W. , Wood, A. J. & Stein, C. M. (2003) G-protein beta(3) Subunit 825C/Tpolymorphism is associated with weight gain during pregnancy. Pharmacogenetics, 13, 241-242.
[97] Terra, S. G. , Mcgorray, S. P. , Wu, R. , Mc Namara D, M. , Cavallari, L. H. , Walker, J. R. , Wallace, M. R. , Johnson, B. D. , Bairey Merz, C, N. , Sopko, G. , Pepine, C. J. & Johnson, J. A. (2005) Association betweenβ-adreneregic receptor polymorphisms and their G-protein-coupled receptors with body mass index and obesity in women:a report from the NHLBI-sponsored WISE Study. Int. J. Obesity. , 29, 746-754.
[98] Siffert W, Rorster P, Jockel KH et al. (1999) Worldwide ethnic distribution of the G-protein Beta-3 subunit 825T allele and its association with obesity in Caucasian, Chinese and Black African individuals. J Am Soc Nephrol. , 10(9):1921-1930.
[99] Neer, E. , Clapham, D. (1988) Roles of G protein subunits in transmembrane signaling. Nature. , 333, 129-134.
[100]Fuller, G. , Shield, S. D. (1998) Molecular basis of medical cell biology. Appleton & Lange, London. , 233-245.
[101]Rosskopf, D. , Busch, S. , Man they I et al(2000) G protein beta 3 gene:Structure, promoter and additional polymorphisms. Hypertension. , 1, 33-41.
[102]Greegorz, D. , PatrycJa, G. S. , Andrzej, P. , et al. (2002) G-proteinβ3 subunit gene C825T polymorphism is associated with arterial hypertension in Polish patients with type 2 diabetes mellitus, Med, Sci, Mouit, 8(8), CR597-602.
[103]Mitchell, A. , Luckebergfeld, B. , Bulumann, S. , et al. (2004) Effect of systemic endothelin A receptor antagonism in various vascular beds in men:in vivo interactions of the major blood pressure-regulating systems and association with the GNB3 polymorphism, Clin Pharmacol Ther, 76(6):396-408.
[104]Danoviz, M. , Pereira, A. , Mill, J. , et al. (2006) Hypertension, obesity and gnb3 gene variants, Clin Exp Pharmacol Physiol, 33(3):248-252.
[105]Ferrari, P. , Ferrandi, M. , Valentini, J. , et al. (2006) Rostafuroxin:an ouabain antagonist that corrects renal and vascular Na-K-ATPase alterations in ouabain and adducin-dependent hypertension, Am J Physiol Regul Integr Comp Physiol, 290(3):R529-535.
[106]Sartori, M. , Parotto, E. , Ceolotto, G. , et al. (2004) C825T polymorphism of the GNB3 gene codifying the G-protein beta-3 subunit and cardiovascular risk, Ann Ital Med Int, 19(4):240-248.
[107]Ogimoto, A. (2004) Polymorphism in guanine nucleotide-bin ding protein (G-protein) beta 3 subunit (GNB3) gene as a risk factor in the development ofhypertensive organ damage, Nippon Rinsho 62(Suppl 3):126-130.
[108]Von Beckerath, N. , Schusterschit, Z. Y. , Koch, W. , et al. (2003) G protein beta 3 subunit 825T allele carriage and risk of coronary artery disease, Atherosclerosis, 167(1):135-139.
[109]Kanai N, Fujii T, Saito K, et al, (1994) Rapid and simple method for preparation of genomic DNA from easily obtainable clotted blood. Clin Pathol, 47:1043-1044.
[110]Neer, E. L. (1995) Heterotrimeric G proteins:organizer of transwenbrane signals, Cell, 80:249-257.
[111]Hamm, A. E. The many faces of G protein signaling, J Biol Chem, 1998, 273:669-672.
[112]Siffert, W. , Rosskopf, D. , Moritz, A. (1995) Enhanced G protein activation in immortalized lymphoblasts from patients with essential hypertension. J Clin Invest, 96:759-766.
[113]Suwazono, Y. , Okubo, Y. , Kobayashi, E. , Miura, K. , Morikawa, Y. , Ishizaki, M. , Kido, T. , Nakagawa, H & Nogawa, K. (2004a) Lack of association between human G-protein beta 3 subunit variant and overweight in Japanese workers. Obes, Res. , 12, 4-8.
[114]Suwazono, Y. , Okubo, Y. , Kobayashi, E. , Miura, K. , Morikawa, Y. , Ishizaki, M. , Kido, T. , Nakagawa, H & Nogawa, K. (2004b) Lack of association of human G-protein beta 3 subunit variant with hypertension in Japanese Workers. J. Hypertens. , 22, 493-500.
[115]Buchmayer, H. , Sunder-Plassmann, G. , Hirschl, M. , et al(2000) G-protein beta 3 subunit gene (GNB3) polymorphism 805C/T in patients with hypertensive crisis. Critical Care Medicine, 9:3203-3206.
[116]Tsai, C. , Yeh, H. , Chon, Y. , et al(2000) G protein beta 3 subunit variant and essential hypertension in Taiwain;a case-control study. Int J of Cavdiol, 2:191-195.
[117]Poch, E. , Gonzales, D. , Gomez-Angelats, E. (2000) G-protein beta(3) subunit gene variant and left ventricular hypertrophy in essential hypertension, Hypertension, 1(part2):214-218.
[118]Von Beckerath, N. , Kastari, A. , Koch, W. , et al. (2000) G protein beta 3 subunit polymorphism and risk of thrombosis and restenosis following coronary stant placement, Athe- rosclerosis, 149(1):151-155.
[119]Siffert, W. , Forster, P. , Jockel, K. , Mvere, D. , et al(1999) World wide ethnic distribution of the G protein beta 3 subunit 825 T allele and its association withobesity in Caucasian, Chinese and Black African. J Amer Soc Nephrol, 9:1921-1930.
[120]Dalgaard LT, Pedersen O. Uncoupling proteins:functional characteristics and role in the pathogenesis of obesity and TypeⅡdiabetes[J]. Diabetologia. 2001, 44:946- 965.
[121]姜文锡,邱长春,程祖亨,等. ApoB基因3'端VNTR多态性与中国新疆维吾尔族自然长寿的比较研究[J].中华医学遗传学杂志. 2006 Oct;23(5):523-7.
[122]玛依拉·吾甫尔,方鸣武,程祖亨,等.载脂蛋白E基因多态性与新疆维吾尔族相关性研究[J].中华医学遗传学杂志. 2005, 22(4):462-463.
[123]Atzmon G, Rincon M, Schechter CB, et al. Lipoprotein genotype and conserved pathway for exceptional longevity in humans[J]. PLoS Biol. 2006, 4(4):562-569.
[124]Stakias N, Liakos P, Tsiapali E, et al. Lower prevalence of epsilon 4 allele of apolipoprotein e gene in healthy, longer-lived individuals of hellenic origin[J]. J Gerontol A Biol Sci Med Sci. 2006, 61 (12):1228-31.
[125]Seripa D, Franceschi M, Matera MG, et al. Sex differences in the association of apolipoprotein E and angiotensin-converting enzyme gene polymorphisms with healthy aging and longevity:a population-based study from Southern Italy[J]. J Gerontol A Biol Sci Med Sci. 2006, 61 (9):918-23.
[126]Edited by vital statistics governmental department of State Statistics Bureau. Annual report forms of China vital statistics[M]. Beijing:China statistics publishing company, 1993:52.
[127]Shifman S, Kuypers J, Kokoris M, et al. Linkage disequilibrium patterns of the human genome across populations[J]. Human Molecular Genetics. 2003, 12(7):771-776.
[128]Horne BD, Camp NJ. Principal component analysis for selection of optimal SNP sets that capture instragenicgenetic variation[J]. Genet Epidemiol. 2004, 26:11-21.
[129]何云刚,金力,黄薇.单核苷酸多态性与连锁不平衡研究进展基础医学与临床[J]. 2004, 24(5):487-490.
[130]Oberkofler H, Iglseder B, Klein K, et al. Associations of the UCP2 gene locus with asymptomatic carotid atherosclerosis in middle-aged women[J]. Arterioscler, Thromb, and Vasc Biol. 2005, 25:604-610.
[131]Dhamrait SS, Stephens J W, Cooper J A, et al. Cardiovascular risk in healthy men and markers of oxidative stress in diabetic men are associated with common variation in the gene for uncoupling protein 2[J]. European Heart Journal. 2004,25:468-475.
[132]陈晓燕,李山,秦雪.人类肿瘤中的线粒体DNA突变.应用预防医学, 2007,2: 57-59.
[133]Coskun PE, Pesini ER, Wallace DC. Control region mtDNA variants:longevity, climatic adaptation, and forensic conondrum[J]. Proc Natl Acad Sci USA, 2003, 100(6):2174.
[134]Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging[J]. Cell, 2005, 120(4):483-495.
[135]Chein KR, Karsent YG. Longevity and lineages:toward the integrative biology of degenerative diseases in heart, muscle, and bone[J]. Cell, 2005, 120(4):533-544.
[136]Feng CS, Ma HC, Yue Y, et al. Effect of propofol on the activation of nuclear factor kappaB and expression of imflammatory cytckines in ceveral cortex during transient focal ischemia in Parkinson:experiment in rats[J]. Zhonghua Yixue Zazhi, 2004, 84(24):2110.
[137]Trifunovi CA, Wredenberg A, Falkkenber GM, et al. Premature aging in mice expressing defective mitochondrial DNA polymerase[J]. Nature, 2004, 429(6990): 417-423.
[138]Kokaza A, Ishikawa M, Matsunaga N, et al. Longevity-associated mitochondrial DNA 5178A/C polymorphism and blood pressure in the Japanese population[J]. Hum Hypertens, 2004, 18:41-45. .
[139]Anderson S, Bankier AT, Barrell BG, et al. Sequence and organization of the human mitochondrial genome[J]. Nature, 1981, 290:457-465.
[140]Criscuolo F, Gonzalez-Barroso MM, Maho YL, et al. Avian uncoupling protein expressed in yeast mitichondria prevents endogenous free radical damage[J]. Proc R Soc B. 2005, 272:803-810.
[141]Driver C, Georgiou G. The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster[J]. Biogerontology, 2004, 5(3):185-92.
[142]Wolf G. Calorie restriction increase life span:a molecular mechanism[J]. Nutr Rev. 2006, 64:89-92.
[143]Ingram DK, Zhu M, Mamczarz J, te al. Calorie restriction mimetics:an emerging research field[J]. Aging Cell. 2006, 5(2):97-108.
[144]Navaro A, Gomes C, Lopez-Cepero MJ, te al. Beneficial effects of moderate exercise on mice aging:survival, behavior, oxdative stress, and mitochondrial electron transfer[J]. Am J Physiol Regul Integr Comp Physiol. 2004,286:R505-R511.
[145]Wallace D C. Mitochondrial genetics:a paradigm of metabolic and degenerative disease, aging, and cancer:A dawn for evolutionary medicine[J]. Annu Rev Genet, 2005, 39:259-407.
[146]De Benedictis G, Rose G, Carrieri G, et al. Mitochondrial DNA inharited variants are associated with successful aging and longevity in humans. FASEB J 1999;13:1532- 1536.
[147]Ivanova R, Lepage V, Charron D, Schachter F. Mitochondrial genotype associated with French Caucasian centenarians. Gerontology 1998;44:349.
[148]Ross OA, McCormack R, Curran MD, et al. Mitochondrial DNA polymorphism:its role in longevity of the Irish population. Exp Gerontol 2001;36:1161-1178.
[149]Niemi AK, Hervonen A, Hurme M, Karhunen PJ, Jylha M, Majiamaa K. Mitochondrial DNA polymorphisms associated with longevity in a Finnish population. Hum Genet 2003;112:29-33.
[150]Matsunaga H, Tanaka Y, Tanaka M, et al. Antiatherogenic mitochondrial genotype in patients with type 2 diabetes. Diabetes Care 2001;24:500-3.
[151]Kokaza A, Ishikawa M, Matsunaga N, et al. Association of the mitochondrialDNA 5178A/C polymorphism with serum lipid levels in the Japanese population. Hum Genet, 2001, 109(5):521
[152]Wang D, Taniyama M, Suzuki Y, et al. Association of the mitochondrial DNA 5178 A/C polymorphism with maternal inheritance and onset of type 2 diabetes in Japanese patients. Exp Clin Endocrinol Diabetes, 2001(109):361.
[153]Kokaza A, Ishikawa M, Matsunaga N, et al. Longevity-associated mitochondrialDNA 5178A/C polymorphism is associated with fasting plasma glocuse levels and glocuse tolerance in Japanese men. Mitochondrion, 2005, 5(6):418.
[154]Song XY, Lu B, Dong XH, et al. Association of the mitochondrial DNA 5178 A/C polymorphism with diabetic nephropathy in Chinese type 2 diabetic patients. Fudan Univ J Med Sci 2006, 33(4):479-482.
[155]Momiyama Y, Fuurutani M, Suzuki Y, et al. A mitichondrial DNA variant associated with left ventricular hypertrophy in diabetes. Biochem Biophys Res Commun, 2003, 312(3):858-864.
[156]Lenaz G, D’Aurelio M, Pich MM, et al. Mitochondrial bioenergetics in aging. Biochim Biophys Acta 2000;1459:397-404.
[157]Cann RL, Stoneking M, Wilson AC. Mitochondrial DNA and human evolution. Nature, 1987;325:31-36.
[158]Shimokata H, Yamada Y, Nakagawa M, et al. Distribution of genetic disease-related genotypes in the National Institute for Longevity Science, Longitudinal Study of Aging(NILS-LSA). J Epidemiol, 2000;10:S46-S55.
[159]Tanaka M. Mitochondrial genotypes and cytochromeb variants associated with longevity on Parkinson, s disease[J]. J Neurol, 2002, 249(supply 2):1111.
[160]Kato T, Kunugi H, Nanko S et al. Association of bipolar disorder with the 5178 polymorphism in mitochondrial DNA. Am J Med Gen 2000;96:182-186.
[161]Kato CH, Umekage T, Tochigi M et al. Mitochondrial DNA polymorphisms and extraversion. Am J Med Gen PartB 2004;128B:76-79.
[162]Holt IJ, Harding AE, Morgan-Hughes JA. Mitochondrial DNA deletion in mitochondrial myopathy[J]. Nature 1988;331:717-719.
[163]Howell N, Miller NR, Mackey DA, et al. Lightning Strikes Twice:Leber Hereditary Optic Neuropathy Families with Two Pathogenic mtDNA Mutations[J]. Neuro-Ophthalmology, 2002, 22(4):262-269.
[164]Linnane AW, Marzuki S, Ozawa T, Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative disease[J]. Lancet 1989, I, 642-645.
[165]Barja G, Herrero A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals[J]. The FASEB Journal. 2000, 14:312-318.
[166]Driver C, Georgiou A, Georgiou G. The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster[J]. Biogerontology. 2004, 5(3):185-92.
[167]Rebrin I, Sohal RS. Comparison of thiol redox state of mitochondria and homo- genates of various tissues between two strains of mice with different longevities[J]. Exp Gerontol. 2004, 39(10):1513-1519.
[168]Brunet-Rossinni AK. Reduced free-radical production and extreme longevity in the little brown bat (Myotis lucifugus) versus two non-flying mammals[J]. Mech Ageing Dev. 2004, 125 (1):11-20.
[169]Kovalenko SA, Tanaka M, Yoneda M, et al. Accumulation of somatic nucleotide substitutions in mitochondrial DNA associated with the 3243 A-to-G tRNA(leu)(UUR) mutation in encephalomyopathy and cardiomyopathy[J]. BiochemBiophys Res Commun 1996, 222:201-207.
[170]Lenaz G, D’Aurelio M, Pich MM, et al. Mitochondrial bioenergetics in aging. Biochim Biophys Acta 2000;1459:397-404.
[171]Qun Chen, Vazquez EJ, Moghaddas S, et al. Production of reactive oxygen species by mitochondria:central role of complexⅢ. J Biol Chem, 2003;278(38):36027.
[172]. Wallace D C. Mitochondrial genetics:a paradigm for aging and degenerative disease? Science 1992;256:628-632.
[173]Kang D, Hamasaki N. Alterations of mitochondrial DNA in common diaseses and diasese states:aging, neurodegeneration, heart failure, diabetes, and cancer. Curr Med Chem 2005;12(4):429-441.
[174]Kato T, Kunugi H, Nanko S et al. Mitochondrial DNA polymorphisms in bipolar disorder. J Affect Disord 2001;61:151-164.
[175]Cortopassi G A, Shibata D, Soong N W et al. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA 1992;89:7370-7374.
[176]Melov S, Shoffner J M, Kaufman A et al. Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle. Nuecleic Acids Res 1995;23:4122-4126.
[177]Kadenbach B, Muncher C, Frank V et al. human aging is associated with stochastic somatic mutations of mitochondrial DNA. Mutat Res 1995;338:161-172.
[178]Larson N G, Clayton D A. Molecular genetic aspects of human mitochondrial disorders. Annu Rev Genet 1995;29:151-178.
[179]Kamazawa A, Nishio Y, Kashiwagi A, et al. Reduced activity of mtDNA decrease the transcription in mitochondria isolated from diabetic rat heart. Am J Physiol Endocrinol Metab 2002;282(4);E778-85.
[180]Wallace D C. Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci USA 1994;91:8739-8746.
[181]Khan SM, Bennett JP Jr. Development of mitichondrial gene replacement therapy. J Bioenerg Biomembr, 2004;36(4):387-393.
[182]Wallace D C. Mitochondrial disease in man and mouse. Science 2000;283(5407):1482-1488.
[183]Michael R A, Richard G H. Mitochondrial influence on aging rate in Caenorhabditis elegans. Aging Cell 2004;3:29-34.
[184]Bartnik E, Lorenc A, Mroczek K. Human mitochondria in health, disease, aging andcancer. J Appl Genet 2001;42(1):65-71.
[185]Wei Y H, Lee H C. Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood) 2002, 227(9):671-682.
[186]De Grey A D. A proposed refinement of the mitochondrial free radical theory of aging. Bio Essays 1997;19:161-166.
[187]De Grey A D. The reductive hotspot hypothesis:un update. Arch Biochem Biophys 2000;373:295-301.
[188]Brunk U T, Terman A. The mitochondrial-lysosomal axis theory of aging:accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem 2002;269:1996-2002.
[189]Brand F N, Kiely D, Kannel W B et al. Family patterns of coronary heart disease mortality:the Framingham longevity study. J Epidemiol 1992;45:169-174.
[190]Giles R E, Blanc H, Cann H M et al. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci USA 1980;77:6715-6719.
[191]Borras C, Sastre J, Garcia-Sala D, et al. Mitochondria from females exhibit hiher antioxidant gene expression and lower oxidative damage than males[J]. Free Radic Biol Med, 200334;546-552?
[192]陈晶,潘尚领.线粒体DNA与衰老和长寿.现代医药卫生, 2006, 22(7):991-993.
[193]Niemi AK, Mailaren JS, Tanaka M, et al. Acombination of the common inherited mitochondrial DNA polymorphisms associated with longevity in a Finnish and Japanese subject[J]. Eur J Hum Genet 2005, 13(2):166
[194]Dato S, Passacino G, Rose G, et al. Association of the mitochondrial DNA haplogroup J with longevity is population specific[J]. Eur J Hum Genet 2004, 12(12):1080.
[195]Jazwinski SM. Aging and longevity genes. Acta Biochimica Polonica, 2000, 47(2):269-279.
[196]Rosskopf D, Busch S, Maanthey I, et al. G proteinβ3 gene:structure, promoter, and additional polymorphisms[J]. Hypertens, 2000,36:33-41.
[197]Levine MA, Smallwood PM, Moen PT, et al. Molecular cloning 0fβ3 subunit, a third form of the G proteinβ-subunit polypeptide[J]. Proc Natl Acad Sci USA. 1990;80:2329-2333.
[198]Clapham DE, Neer EJ. G proteinβγsubunits[J]. Annu Rev Pharmacol Toxicol, 1997, 37:167-203.
[199]Sondek J, Bohm A, Lambright DG, et al. Crystal structure of a GA proteinβγdimerat 2. 1 A resolution[J]. Nature, 1996;379:369-374.
[200]Levine MA, Smallwood PM, Moen PT, et al. Molecular cloning ofβ3 subunit, a third from of the Gproteinβ-subunit polypeptide[J]. Proc Natl Acad Sci USA, 1990, 80:2329-2333.
[201]Appel LJ, Champagne CM, Harsha DW, et al. Effects of the PREMIER clinical trial[J]. JAMA, 2003, 289(16):2083-2093.
[202]王淑英.高血压病的预防与健康教育新进展[J].医学综述, 2007, 13:432-434.
[203]王增武,武阳丰,赵连成,等.中国中年人群高血压患病率及知晓率?治疗率?控制率的演变趋势[J].中华流行病学杂志, 2004, 25(5):408.
[204]Beevers G, Lip JY, O, Brien E. ABC of human hypertension;the pathopysiology of hypertension[J]. BMJ, 2001, 322(7291):912-916.
[205]Izawa H, Yamada Y, Okada T, et al. Prediction of genetic risk for hypertension[J]. Hypertension, 2003, 41(3):1035-1040.
[206]Brand E, Hermann SM, Nicaud V, et al. The 825C-T polymorphism of the G protein subunit beta 3 is not related to hypertension[J]. Hypertension, 1999, 33(5):1175-1178.
[207]Hegele RA, Harris SB, Hanley AG, et al. G-protein beta 3 subunit variant and blood pressure variation in Canadian Oji-Gree[J]. Hypertens, 1998, 32:688-692.
[208]Schorr U, Blaschke K, Beige J, et al. G protein beta 3 subunit C825T allele and response to dietary salt in normotensive men[J]. J Hypertens, 2000, 18:855-859.
[209]Biao L, Dong LG, Yue LW, et al. G-protein beta 3 subunit gene variants and essential hypertension in the northen Chinese Han population[J]. Ann Hum Genet, 2005, 69:468-73.
[210]Huang X, Ju Z, Song Y, et al. Lack of association between G-protein beta 3 subunit gene and essential hypertension in Chinese:a case-control and a family-based study[J]. J Mol Med, 2003, 81:729-735.
[211]Bluthner K, Schmidt S, Siffert W, et al. increased frequency of G protein beta-3 subunit 825T allele in dialyzed patients with type diabetes[J]. Kidney Int, 1999, 55:1247-1250.
[212]Pietruck F, Spleiter S, Daul A, et al. Enhanced G protein activation in IDDM patients with diabetic nephropathy[J]. Diabetologia, 1998, 41:94-100.
[213]Viard P, Exner T, Maier U, et al. G betagamma dimers stimulate vascular L-type Ca2+ channels via phosphoinositide 3-kinase[J]. FAS EB J, 1999, 13(6):685-694.
[214]Jin J, Kunapuli SP. Coactivation of two different G protein–coupled receptors isessential for ADP-induced platelet aggregation[J]. Proc Natl Acad Sci USA, 1998, 95:8070-74.
[215]Von Beckerath, N. , Kastari, A. , Koch, W. , et al. G protein beta 3 subunit polymorphism and risk of thrombosis and restenosis following coronary stant placement[J]. Athe- rosclerosis, 2000, 149(1):151-155.
[216]Hengstenberg C, Schunkert H, Mayer B, et al. Association between a polymorphism in the G protein beta 3 subunit gene with arterial hypertension but not with myocardial infraction[J]. Cardiovasc Res, 2001, 49(4):820-827.
[217]Comuzzie AG, Allison DB. The search for human obesity genes[J]. Science, 1998, 280(5368):1374-1377.
[218]Poch E, Giner V, Gonzalez-Nunez D, et al. Association between a polymorphism in the G protein beta 3 subunit T allele with insulin resistance in essential hypertension[J]. Clin Exp Hypertens, 2002, 24(5):345-353.
[219]楼晓明,朱心强,秦建芬,等. GNB3基因C825T位点多态性与肥胖相关性[J].上海交通大学学报(医学版), 2006, 26(8):895- 898.
[220]Robert A, Anderson C, Young TK, et al. G protein beta 3 subunit gene splice variant and body fat distribution in Nunavut Inuit[J]. Genome Research, 1999, 9:972-977.
[221]Grzegorz D, Patrycja GS, Andrzej P, et al. G-protein beta 3 subunit gene C825T polymorphism is associatedwith arterial hypertension in Polish patients with type2 diabetes mellitus[J]. Med Sci Monit, 2002, 8(8):CR597-602.
[222]Strojek K, Grzeszczak W, Morawin E, et al. Nephropathy of typeII diabetis:Evidence for hereditary factors[J]?Kidney Int, 1997, 51:1602-1607.
[223]Fernandez RJ, Penarroja G, Richart C, et al. G protein beta-3 subunit 825T allele predicts improvement of insulin sensitivity and nitric oxide sensitivity in type2 diabetes mellitus[J]. Diabetes, 20001, 50(suppl 2):A289.
[224]Kiani JG, Saeed M, Parvez SH, et al. Association of G protein beta-3 subunit gene(GNB3) 825T allele with typeII diabetes[J]. Neuro Endocrinol Lett, 2005, 26(2):87-88.
[225]何燕,钟国强.原发性高血压后选基因的研究进展[J].医学综述, 2006, 12(18):1104-1106.
[226]Siffert, W, Rosskopf, D, Erbel R. Genetic polrmorphism of the G-protein beta 3 subunit, obesity and essential hypertension[J]. Herz, 2000, 25(1):26-33.
[227]王鸿懿,孙宁玲. GNB3基因多态性与心血管疾病[J].中国医师杂志, 2002增刊:383-385.
[1] Harman D. Aging[J]. Ann N Y Acad Sci. 2001, 928:1-21.
[2] Barja G. Free radicals and aging[J]. Trends Neurosci. 2004, 27(10):595-600.
[3] Criscuolo F, Gonzalez-Barroso MM, Maho YL, et al. Avian uncoupling protein expressed in yeast mitichondria prevents endogenous free radical damage[J]. Proc R Soc B. 2005, 272:803-810.
[4] Driver C, Georgiou G. The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster[J]. Biogerontology, 2004, 5(3):185-92.
[5] Wolf G. Calorie restriction increase life span:a molecular mechanism[J]. Nutr Rev. 2006, 64:89-92.
[6] Ingram DK, Zhu M, Mamczarz J, te al. Calorie restriction mimetics:an emerging research field[J]. Aging Cell. 2006, 5(2):97-108.
[7] Navaro A, Gomes C, Lopez-Cepero MJ, te al. Beneficial effects of moderate exercise on mice aging:survival, behavior, oxdative stress, and mitochondrial electron transfer[J]. Am J Physiol Regul Integr Comp Physiol. 2004, 286:R505-R511.
[8] Tanaka M, Gong JS, Zhang J, et al. Mitochondrial genotype associated with longevity and its inhibitory effect on mutagenesis. Mech[J]. Ageing Dev 2000;116:65-76.
[9] Anderson S, Bankier AT, Barrell, et al. Sequence and organization of the human mitochondrial genome[J]. Nature. 1981, 290:457-465.
[10] Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K. Mitochondrial genotype associated with longevity[J]. Lancet 1998;351:185-186.
[11] Holt IJ, Harding AE, Morgan-Hughes JA. Mitochondrial DNA deletion in mitochondrial myopathy[J]. Nature 1988;331:717-719.
[12] Howell N, Miller NR, Mackey DA, et al. Lightning Strikes Twice:Leber Hereditary Optic Neuropathy Families with Two Pathogenic mtDNA Mutations[J]. Neuro-Ophthalmology, 2002, 22(4):262-269.
[13] Tanaka M, Ino H, Ohno K, et al. Mitochondrial DNA mutations in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes(MELAS)[J]. Biochem Biophys Res Commun 1991;174:861-868.
[14] Linnane AW, Marzuki S, Ozawa T, Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative disease[J]. Lancet 1989, I,642-645.
[15] Barja G, Herrero A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals [J]. The FASEB Journal. 2000, 14:312-318.
[16] Driver C, Georgiou A, Georgiou G. The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster [J]. Biogerontology. 2004, 5(3):185-92.
[17] Rebrin I, Sohal RS. Comparison of thiol redox state of mitochondria and homo- genates of various tissues between two strains of mice with different longevities [J]. Exp Gerontol. 2004, 39(10):1513-1519.
[18] Brunet-Rossinni AK. Reduced free-radical production and extreme longevity in the little brown bat (Myotis lucifugus) versus two non-flying mammals [J]. Mech Ageing Dev. 2004, 125 (1):11-20.
[19] Kovalenko SA, Tanaka M, Yoneda M, et al. Accumulation of somatic nucleotide substitutions in mitochondrial DNA associated with the 3243 A-to-G tRNA(leu)(UUR) mutation in encephalomyopathy and cardiomyopathy[J]. Biochem Biophys Res Commun 1996, 222:201-207.
[20] Torroni A, Huoponen K, Francalacci p, tet al. Classification of European mtDNAs from analysis of three European populations[J]. Genetics 1996, 144:1835-1850.
[21] Van Den Bosch BJ, et al. Mutation analysis of the entire mitochondrial genome using denaturing high performance liquid chromatography[J]. Nucleic Acid Research, 2000, 28(20):E89.
[22]孙生,张惠芹,刘宗伟?当前线粒体DNA研究及在法医学中的应用[J].中国人民公安大学学报(自然科学版), 2006, 47:28-32.
[23] Gill P, Inavo PL, Kimpton C, et al. Identification of the remains of the Romanov family by DNA analysis[J]. Nat Genet, 1994, 6:130-135.
[24] Alexeyev MF, Lecloux SP, Wilson GL. Mitochondial DNA and aging[J]. Clinical Science. 2004, 107:355-364.
[25] Howell N, Kubacka I, Mackey DA. How rapidly does the human mitochondrial genome evolve[J]? Am J Hum Genet 1996, 59:501-9.
[26] Parsons TJ, Muniec DS, Sullivan K, et al. A high observed substitution rate in the human mitochondrial DNA control region[J]. Nat Gnet 1997, 15:363-8.
[27] Schon EA, Bonilla E, Dimaoru S. Mitochondrial DNA mutations and pathogenesis[J]. Bioenerg Biomembr 1997, 29:131-49.
[28] Dato S, Passarino G, Rose G, et al. Association of the mitochondrial DNA haplogroup J with longevity is population specific[J]. Eur J Hum Genet. 2004, 12(12):1080-2.
[29] Santoro A, Salvioli S, Raule N, et al. Mitochondrial DNA involvement in human longevity [J]. Biochim Biophys Acta. 2006, 1757(9-10):1388-99.
[30] Qun Chen, Vazquez EJ, Moghaddas S, et al. Production of reactive oxygen species by mitochondria:central role of complexⅢ. J Biol Chem, 2003;278(38):36027.
[31] Wallace D C. Mitochondrial genetics:a paradigm of metabolic and degenerative disease, aging, and cancer:A dawn for evolutionary medicine[J]. Annu Rev Genet, 2005, 39:259-407.
[32] Kang D, Hamasaki N. Alterations of mitochondrial DNA in common diaseses and diasese states:aging, neurodegeneration, heart failure, diabetes, and cancer. Curr Med Chem 2005;12(4):429-441.
[33] Jazwinski SM. Yeast longevity and aging-the mitochondrial connection [J]. Mech Ageing Dev. 2005, 126(2):243-248.
[34] Kato CH, Umekage T, Tochigi M et al. Mitochondrial DNA polymorphisms and extraversion[J]. Am J Med Gen PartB 2004;128B:76-79.
[35] Lack of correlation between mitochondrial reactive oxygen species production and life span in Drosophila[J]. Ann N Y Acad Sci. 2004, 1019:388-391.
[36] Corral-Debrinski M, Horton T, Lott MT, et al. Mitochondtial DNA deletions in human brain:regional variability and increase with advanced age[J]. Net Genet 1992, 2:324-9.
[37] Mashima Y, Kimura Y, Yamamoto Y, et al. Optic disc excavation in the atrophic stage of Leber, s hereditary optic neuropathy:comparison with normal tension glaucoma[J]. Greafes Arch Clin Exp Ophthalmol, 2003, 241:75-80.
[38]韦企平,孙艳红,宫晓红,等.中国人Leber遗传性视神经病变线粒体DNA突变的主要类型和临床特点[J].中华眼底病杂志, 2004, 20(2):78-80.
[39] Borras C, Sastre J, Garcia-Sala D, et al. Mitochondria from females exhibit hiher antioxidant gene expression and lower oxidative damage than males[J]. Free Radic Biol Med, 2003, 34;546-552.
[40] Carelli V. Leber, s hereditary optic neuropathy. In:Schapira AHV, DiMauro S. Mitochondrial Disorders in Neurology 2nd Edition. Boston:Butterworth-Heinemann, 2002, 115-142.
[41] Edland SD, Silverman JM, Peskind ER, et al. Increased risk of dementia in mothersof Alzheimer, s disease cases:evidence for maternal inheritance[J]. Neurology 1996, 47:254-6.
[42] Wooten GF, Currie LJ, Bennett JP, et al. Maternal inheritance in Parkenson, s disease[J]. Ann Neurol 1997, 41:265-8.
[43] Kosel S, Hofhaus G, Maassen A, et al. Role of mitochondrial in Parkenson, s disease[J]. Biol Chem, 1999, 380(7-8):865-870.
[44] Swerdlow RH, Parks JK, Cassarino DS, et al. Cybrids in Alzheimer, s disease:a cellular model of the disease[J]? Neurology 1997, 49:918-25.
[45] Hutchin T, Cortopassi GA. Mitochondrial DNA clone is associated with increased risk for Alzheimer, s disease [J]. Proc Natl Acad Sci USA, 1995, 92(15):6892-6895.
[46] Coskun PE, Ru Iz-pesin IE, Wallace DC. Control region mtDNA variats:longevity, climatic adaptation, and a forensic conundrum[J]. Proc Natl Acad Sci USA, 2003, 100(5):2174-2176.
[47] Hutchin TP, Heath PR, Pearson RC, et al. Mitochondrial DNA mutations in Alzheimer, s disease [J]. Biochim Biophys Res Commun 1997, 241:221-5.
[48] Cortopassi G A, Shibata D, Soong N W et al. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA 1992;89:7370-7374.
[49] Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging[J]. Cell 2005, 120(4):483-495.
[50] Chien KR, Karsenty G. Longevity and lineages:toward the integrative biology of degenerative diseases in heart, muscle, and bone[J]. Cell, 2005, 120(4):533-544.
[51] Davis RE, Miller S, Herrnstadt C, et al. Mutations in mitochondrial cytchrome c oxidase genes segregate with late-onset Alzheimer, s disease [J]. Proc Natl Acad Sci USA 1997, 94:4526-31.
[52] Pesce V, Connio A, Fracasso F. Age-related mitochondrial genotypic and phenotypic alterations in human skeletal muscle[J]. Free Radic Biol Med 2001, 30(11):607-17.
[53] Melov S, Shoffner J M, Kaufman A et al. Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle. Nuecleic Acids Res 1995;23:4122-4126.
[54] Hegele RA, Zinman B, Hanley AJG, et al. A commom mtDNA polymorphism associated with variation in plasma triglyceride concentration[J]. Am J Hum Genet 1997, 60:1552-5.
[55] Wallace D C. Mitochondrial disease in man and mouse. Science2000;283(5407):1482-1488.
[56] Michael R A, Richard G H. Mitochondrial influence on aging rate in Caenorhabditis elegans. Aging Cell 2004;3:29-34.
[57] Kato T, Kunugi H, Nanko S et al. Mitochondrial DNA polymorphisms in bipolar disorder. J Affect Disord 2001;61:151-164. Miwa S, Riyahi K, Partridge L, et al.
[58] Khan SM, Bennett JP Jr. Development of mitichondrial gene replacement therapy. J Bioenerg B, 2004;36(4):387-393.
[59] Wallace D C. The mitochondrial genome in human adaptive radiation and disease:on the road to therapeutics and performance enhancement[J]. Gene, 2005;354:169-180.
[60] Seo BB, Nakamaru-ogisu E, Cru ZP, et al. Functional expression of the single subunit NADH dehydrogenase in mitochondria in vivo:a potential therapy for complex I deficiencies[J]. Hum Gene Ther, 2004, 15(9):887-895.
[1] Appel LJ, Champagne CM, Harsha DW, et al. Effects of the PREMIER clinical trial[J]. JAMA, 2003, 289(16):2083-2093.
[2]王淑英.高血压病的预防与健康教育新进展[J].医学综述, 2007, 13:432-434.
[3]王增武,武阳丰,赵连成,等.中国中年人群高血压患病率及知晓率?治疗率?控制率的演变趋势[J].中华流行病学杂志, 2004, 25(5):408.
[4] Beevers G, Lip JY, O, Brien E. ABC of human hypertension;the pathopysiology of hypertension[J]. BMJ, 2001, 322(7291):912-916.
[5] Taroh liri, Bourne HR. G proteins propel surprise[J]. Nature Genetics, 1998, 18(1):8-10.
[6] Siffert, W. G-protein beta 3 subunit 825T allele and hypertension[J]. Curr Hypertens. Rep. 2003, 5:47-53.
[7] Rosskopf D, Busch S, Maanthey I, et al. G proteinβ3 gene:structure, promoter, and additional polymorphisms[J]. Hypertens, 2000, 36:33-41.
[8] Levine MA, Smallwood PM, Moen PT, et al. Molecular cloning 0fβ3 subunit, a third form of the G proteinβ-subunit polypeptide[J]. Proc Natl Acad Sci USA. 1990;80:2329-2333.
[9] Clapham DE, Neer EJ. G proteinβγsubunits[J]. Annu Rev Pharmacol Toxicol, 1997, 37:167-203.
[10] Sondek J, Bohm A, Lambright DG, et al. Crystal structure of a GA proteinβγdimer at 2. 1 A resolution[J]. Nature, 1996;379:369-374.
[11] Hamet P, Pausova Z, Adaricher V, et al. Hypertension:genes and environment[J]. J Hypertens, 1998, 16:397-418.
[12] Siffert, W. , Rosskopf, D. , Siffert, G. , Busch, S. , Moritz, A. , Erbel. R. , Sharma, A. M. , Rit2, E. , Wichmavn, H. E. , Jadobs, K. H. & Hors themke, B. Association of a human G-protein beta 3 subunit variant with hypertension[J]. Nat. Genet, 1998, 18:45-
[13] Beige J, Hohenbleicher H, Distler A, et al. G protein beta 3 subunit C825T variant and ambulatory blood pressure in essential hypertension[J]. Hypertension, 1999, 33(4):1049-1051.
[14] Adam VB, Chery LJ, Dale RN, et al. G-protein beta 3 subunit variant in Causation of essential hypertension[J]. Hypertens, 1998, 32:1094-97.
[15] Dong YB, Zhu HD, Sagnella GA, et al. Association between the C825Tpolymorphism of the G protein beta 3 subunit gene and hypertension in Blacks[J]. Hypertens, 1999, 34:1193-1196.
[16] Ogimoto, A. Polymorphism in guanine nucleotide-binding protein (G-protein) beta 3 subunit (GNB3) gene as a risk factor in the development of hypertensive organ damage[J]. Nippon Rinsho, 2004, 62(Suppl 3):126-130.
[17] Siffert, W. , Forster, P. , Jockel, K. , Mvere, D. , et al(1999) World wide ethnic distribution of the G protein beta 3 subunit 825 T allele and its association with obesity in Caucasian, Chinese and Black African. J Amer Soc Nephrol, 9:1921-1930.
[18] Izawa H, Yamada Y, Okada T, et al. Prediction of genetic risk for hypertension[J]. Hypertension, 2003, 41(3):1035-1040.
[19] Suwazono, Y. , Okubo, Y. , Kobayashi, E. , Miura, K. , Morikawa, Y. , Ishizaki, M. , Kido, T. , Nakagawa, H & Nogawa, K. Lack of association of human G-protein beta 3 subunit variant with hypertension in Japanese Workers[J]. J. Hypertens, (2004b), 22, 493-500.
[20] Tsai, C. , Yeh, H. , Chon, Y. , et al. G protein beta 3 subunit variant and essential hypertension in Taiwain;a case-control study[J]. Int J of Cavdiol, 2000, 2:191-195.
[21] Schorr U, Blaschke K, Beige J, et al. G protein beta 3 subunit C825T allele and response to dietary salt in normotensive men[J]. J Hypertens, 2000, 18:855-859.
[22] Mitchell, A. , Luckebergfeld, B. , Bulumann, S. , et al. Effect of systemic endothelin A receptor antagonism in various vascular beds in men:in vivo interactions of the major blood pressure-regulating systems and association with the GNB3 polymorphism[J]. Clin Pharmacol Ther, 2004, 76(6):396-408.
[23] Danoviz, M. , Pereira, A. , Mill, J. , et al. Hypertension, obesity and gnb3 gene variants[J]. Clin Exp Pharmacol Physiol, 2006, 33(3):248-252.
[24] Mahmood MS, Mian ZS, Afzal A, et al. G protein beta 3 subunit gene 825C>T dimorphism is associated with left ventricular hypertrophy but not essential hypertension[J]. Med Sci Monit, 2005, 11(1):CR6-CR9.
[25] Ferrari, P. , Ferrandi, M. , Valentini, J. , et al. Rostafuroxin:an ouabain antagonist that corrects renal and vascular Na-K-ATPase alterations in ouabain and adducin-dependent hypertension[J]. Am J Physiol Regul Integr Comp Physiol, 2006, 290(3):R529-535.
[26] Sartori, M. , Parotto, E. , Ceolotto, G. , et al. C825T polymorphism of the GNB3 gene codifying the G-protein beta-3 subunit and cardiovascular risk[J]. Ann Ital Med Int, 2004), 19(4):240-248.
[27]董会奕,李秋荣,王勤,等. ADD-1基因和GNB3基因多态性与原发性高血压相关性研究[J].岭南心血管病杂志, 2006, 12(4):258-261.
[28]李庆祥,李风衣,杜如跃,等.长裙地区原发性高血压与G蛋白β3亚单位基因C825T多态性[J].中国微循环杂志, 2006, 10(3):205-207.
[29]呼日勒,赵世刚,牛广明,等. G蛋白β3亚单位基因C825T多态性与蒙古族原发性高血压的相关性研究[J].中国优生与遗传杂志, 2006, 14(12):15-17.
[30] Tanira M, Balushi KL. Genetic variations related to hypertension:a review[J]. J Hum Hypertens, 2005, 19:7-19.
[31] Larson N, Hutchimson R, Boelwinkh E. Lack of association of 3 functional gerle variants with hypertension in African Americans[J]. Hypertension, 2000, 35(6):1297-1300.
[32] Budmmyer H, Sundar-Plassmann G, Hirsch, et al. G protein beta 3 subunit gene (GNB3) polymorphism 825C-T in patients with hypertensive crisis[J]. Crit Care Med, 2000, 28(9):203-206.
[33] Ishikawa K, Imai Y, Katsuya T, et al. Human G-protein beta 3 subunit variant is associated with potassium and total cholesterol levels but not with blood pressure[J]. Am Hypertens, 2000, 13(2):140-145.
[34] Brand E, Hermann SM, Nicaud V, et al. The 825C-T polymorphism of the G protein subunit beta 3 is not related to hypertension[J]. Hypertension, 1999, 33(5):1175-1178.
[35] Hegele RA, Harris SB, Hanley AG, et al. G-protein beta 3 subunit variant and blood pressure variation in Canadian Oji-Gree [J]. Hypertens, 1998, 32:688-692.
[36] Biao L, Dong LG, Yue LW, et al. G-protein beta 3 subunit gene variants and essential hypertension in the northen Chinese Han population[J]. Ann Hum Genet, 2005, 69:468-73.
[37] Huang X, Ju Z, Song Y, et al. Lack of association between G-protein beta 3 subunit gene and essential hypertension in Chinese:a case-control and a family-based study[J]. J Mol Med, 2003, 81:729-735.
[38] Neer, E. L. Heterotrimeric G proteins:organizer of transwenbrane signals[J]. Cell, 1995, 80:249-257.
[39] Kanai N, Fujii T, Saito K, et al. Rapid and simple method for preparation of genomic DNA from easily obtainable clotted blood[J]. Clin Pathol, 1994, 47:1043-1044.
[40] Hamm, A. E. (1998) The many faces of G protein signaling, J Biol Chem, 273:669-672.
[41] Siffert, W. , Rosskopf, D. , Moritz, A. (1995) Enhanced G protein activation in immortalized lymphoblasts from patients with essential hypertension. J Clin Invest, 96:759-766.
[42] Viard P, Exner T, Maier U, et al. G betagamma dimers stimulate vascular L-type Ca2+ channels via phosphoinositide 3-kinase[J]. FAS EB J, 1999, 13(6):685-694.
[43]何燕,钟国强.原发性高血压后选基因的研究进展[J].医学综述, 2006, 12(18):1104-1106.
[44] Siffert, W, Rosskopf, D, Erbel R. Genetic polrmorphism of the G-protein beta 3 subunit, obesity and essential hypertension [J]. Herz, 2000, 25(1):26-33.
[45]王鸿懿,孙宁玲. GNB3基因多态性与心血管疾病[J].中国医师杂志, 2002增刊:383-385.
[46] Jin J, Kunapuli SP. Coactivation of two different G protein–coupled receptors is essential for ADP-induced platelet aggregation[J]. Proc Natl Acad Sci USA, 1998, 95:8070-74.
[47] Von Beckerath, N, Schusterschit, ZY, Koch, W, et al. G protein beta 3 subunit 825T allele carriage and risk of coronary artery disease[J]. Atherosclerosis, 2003, 167(1):135-139.
[48] Von Beckerath, N. , Kastari, A. , Koch, W. , et al. G protein beta 3 subunit polymorphism and risk of thrombosis and restenosis following coronary stant placement[J]. Athe- rosclerosis, 2000, 149(1):151-155.
[49] Hengstenberg C, Schunkert H, Mayer B, et al. Association between a polymorphism in the G protein beta 3 subunit gene with arterial hypertension but not with myocardial infraction[J]. Cardiovasc Res, 2001, 49(4):820-827.
[50]张磊,董硷虎.肥胖体表测量指标与糖尿病及心血管病的研究进展[J].国外医学.内分泌学分册, 2005, 25(4):257-259.
[51] Cao H, Maeda K, Gorgun CZ, et al. Regulation of metabolic responses by adipocyte/macrophage Fatty Acid-binding proteins in leptin-deficient mice[J]. Diabetes, 2006, 55(4):257-259.
[52] Comuzzie AG, Allison DB. The search for human obesity genes[J]. Science, 1998, 280(5368):1374-1377.
[53] Poch E, Giner V, Gonzalez-Nunez D, et al. Association between a polymorphism in the G protein beta 3 subunit T allele with insulin resistance in essential hypertension[J]. Clin Exp Hypertens, 2002, 24(5):345-353.
[54]楼晓明,朱心强,秦建芬,等. GNB3基因C825T位点多态性与肥胖相关性[J].上海交通大学学报(医学版), 2006, 26(8):895- 898.
[55] Robert A, Anderson C, Young TK, et al. G protein beta 3 subunit gene splice variant and body fat distribution in Nunavut Inuit[J]. Genome Research, 1999, 9:972-977.
[56] Grzegorz D, Patrycja GS, Andrzej P, et al. G-protein beta 3 subunit gene C825T polymorphism is associatedwith arterial hypertension in Polish patients with type2 diabetes mellitus[J]. Med Sci Monit, 2002, 8(8):CR597-602.
[57] Strojek K, Grzeszczak W, Morawin E, et al. Nephropathy of typeII diabetis:Evidence for hereditary factors[J]?Kidney Int, 1997, 51:1602-1607.
[58] Bluthner K, Schmidt S, Siffert W, et al. increased frequency of G protein beta-3 subunit 825T allele in dialyzed patients with type diabetes[J]. Kidney Int, 1999, 55:1247-1250.
[59] Pietruck F, Spleiter S, Daul A, et al. Enhanced G protein activation in IDDM patients with diabetic nephropathy[J]. Diabetologia, 1998, 41:94-100.
[60] Fernandez RJ, Penarroja G, Richart C, et al. G protein beta-3 subunit 825T allele predicts improvement of insulin sensitivity and nitric oxide sensitivity in type2 diabetes mellitus[J]. Diabetes, 20001, 50(suppl 2):A289.
[61] Kiani JG, Saeed M, Parvez SH, et al. Association of G protein beta-3 subunit gene(GNB3) 825T allele with typeII diabetes[J]. Neuro Endocrinol Lett, 2005, 26(2):87-88.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |