β_2-AR基因、ACE基因多态性与原发性高血压病并缺血性脑卒中的相关性研究
|
摘要
目的:探讨β2-肾上腺素能受体(β2-AR/-1023)基因G/A多态性(rs2053044)、血管紧张素转换酶(ACE)基因I/D多态性(insertion,I/ deletion, D;rs4646994)与原发性高血压病合并缺血性脑卒中(EH-ICVD)的相关性。
方法:收集原发性高血压病并缺血性脑卒中患者345例(EH-ICVD组),原发性高血压病无脑卒中患者315例(EH-non-ICVD组),及血压正常者255例(Control组)。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和PCR法检测所有受试者β2-AR/-1023(G/A)多态性基因型和ACE(I/D)多态性基因型,采用χ2检验比较三组不同基因型及基因型组合分布频率,Hardy-Weinberg平衡用拟合χ2检验,筛查和调整危险因素用多因素二项或多项Logistic回归分析。
结果:1、Hardy-Weinberg遗传平衡检验示:各组β2-AR基因和ACE基因不同基因型分布符合Hardy-Weinberg遗传平衡(P均>0.05),样本具有群体代表性。
2、EH-ICVD组、EH-non-ICVD组和Control组三组β2-AR基因的AA、AG和GG基因型构成比总的分布有显著性差异(χ2=11.834,P=0.019),经进一步卡方分割检验显示EH-ICVD组AA基因型频率(12.5%)高于EH-non-ICVD组(7.0%)和Control组(5.5%),差异显著(χ2=10.298,P=0.001);三组ACE基因的II、ID和DD基因型构成比总的分布有显著性差异(χ2=16.884,P=0.002),经进一步卡方分割检验显示EH-ICVD组DD基因型频率(20.9%)高于EH-non-ICVD组(14.6%)和Control组(9.4%)(χ2=12.093,P=0.001);三组不同基因组合AA+DD、AG/GG+DD、AA+II/ID、AG/GG+II/ID联合基因型构成比总的分布有显著性差异(χ2=27.814,P<0.001),经进一步卡方分割检验显示EH-ICVD组AG/GG+II/ID联合基因型频率(68.4%)低于EH-non-ICVD组(79.7%)和Control组(85.9%),差异显著(χ2=24.073,P<0.001)。
3.经多因素Logistic回归,筛查出吸烟、血胆固醇、高血压等级、高血压病史、β2-AR-AA基因型、ACE-DD基因型是高血压合并缺血性脑卒中的主要危险因素。其中经调整了其他危险因素的影响后,β2-AR-AA基因型、ACE-DD基因型相对危险度(OR)值分别为1.854(95%CI:1.041-3.301,P=0.036)和1.590(95%CI:1.019-2.481,P=0.041)。
结论:携带有β2-AR-AA基因型、ACE-DD基因型可能是高血压病合并缺血性脑卒中的独立危险因素。
Objective: To investigate the association between polymorphisms of the -1023 region ofβ2-adrenoceptor(β2-AR/-1023) gene-G/A,angiotensin converting enzyme (ACE) gene insertion/deletion(I/D) and essential hypertension(EH) complicated by ischemic cerebrovascular disease(ICVD).
Methods: We collected 345 subjects of EH-ICVD group, 315 subjects of EH without ICVD(EH-non-ICVD) group and 255 subjects of control group.β2-AR/-1023 gene-G/A were determined with the use of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP) methods,ACE gene-I/D polymorphisms were determined with the use of PCR,and polymorphic frequencies were compared in patients with EH-ICVD,EH-non-ICVD group and control. Information about prior exposure to various potential risk factors was also obtained. Chi-square test was used to compare difference of genotypes distribution among the three groups. The Hardy-Weinberg equilibrium was tested by Chi-square test of goodness of fit. Odds ratios for these comparisons of dangerous factors were calculated by Binary and Multinomial Logistic Regression.
Results: 1. The frequencies of different geneotypes ofβ2-AR/-1023 and ACE were in agreement with Hardy-Weinberg equilibrium in our study(P>0.05).
2. Chi-square test showed significant difference forβ2-AR-AA, AG and GG genotypes distribution in the three groups(χ2=11.834,P=0.019), and then Partitions ofχ2 method indicated thatβ2-AR-AA genotype frequencies in EH-ICVD group ( 12.5% ) were significantly higher than those in EH-non-ICVD group(7.0%)and Control group(5.5%) (χ2=10.298,P=0.001). The constituent ratio of ACE-II, ID, DD genotype was significantly different in the three groups(χ2=16.884,P=0.002), and then Partitions ofχ2 method showed that ACE–DD genotype frequencies in EH-ICVD group(20.9%) were significantly higher than those in EH-non-ICVD group(14.6%)and Control group(9.4%)(χ2=12.093,P=0.001). The 2 gene conjoint Analysis indicated significant difference of combined genotype frequencies in the three groups (χ2=27.814,P<0.001), furthermore, and Partitions ofχ2 method showed that AG/GG+II/ID combined genotype frequencies in EH-ICVD group(68.4%) were significantly lower than those in EH-non-ICVD group(79.7%)and Control group(85.9%)(χ2=24.073,P<0.001).
3. Multinomial Logistic-regression Analysis indicated that Smoke,Cholesterol, Blood Pressure Level,Blood Pressure Period,β2-AR-AA genotype,ACE-DD genotype were risk factors for EH-ICVD.The odds ratios(OR) of theβ2-AR-AA genotype vs AG/GG and ACE-DD genotype vs II/ID for EH-ICVD were 1.854 (95%CI:1.041-3.301,P=0.036) and 1.590 (95%CI:1.019-2.481, P=0.041) after adjusting other confounding factors, respectively.
Conclusion:β2-AR-AA and ACE-DD genotype may be the independent risk factors of hypertensive patients with ischemic cerebrovascular disease.
方法:收集原发性高血压病并缺血性脑卒中患者345例(EH-ICVD组),原发性高血压病无脑卒中患者315例(EH-non-ICVD组),及血压正常者255例(Control组)。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和PCR法检测所有受试者β2-AR/-1023(G/A)多态性基因型和ACE(I/D)多态性基因型,采用χ2检验比较三组不同基因型及基因型组合分布频率,Hardy-Weinberg平衡用拟合χ2检验,筛查和调整危险因素用多因素二项或多项Logistic回归分析。
结果:1、Hardy-Weinberg遗传平衡检验示:各组β2-AR基因和ACE基因不同基因型分布符合Hardy-Weinberg遗传平衡(P均>0.05),样本具有群体代表性。
2、EH-ICVD组、EH-non-ICVD组和Control组三组β2-AR基因的AA、AG和GG基因型构成比总的分布有显著性差异(χ2=11.834,P=0.019),经进一步卡方分割检验显示EH-ICVD组AA基因型频率(12.5%)高于EH-non-ICVD组(7.0%)和Control组(5.5%),差异显著(χ2=10.298,P=0.001);三组ACE基因的II、ID和DD基因型构成比总的分布有显著性差异(χ2=16.884,P=0.002),经进一步卡方分割检验显示EH-ICVD组DD基因型频率(20.9%)高于EH-non-ICVD组(14.6%)和Control组(9.4%)(χ2=12.093,P=0.001);三组不同基因组合AA+DD、AG/GG+DD、AA+II/ID、AG/GG+II/ID联合基因型构成比总的分布有显著性差异(χ2=27.814,P<0.001),经进一步卡方分割检验显示EH-ICVD组AG/GG+II/ID联合基因型频率(68.4%)低于EH-non-ICVD组(79.7%)和Control组(85.9%),差异显著(χ2=24.073,P<0.001)。
3.经多因素Logistic回归,筛查出吸烟、血胆固醇、高血压等级、高血压病史、β2-AR-AA基因型、ACE-DD基因型是高血压合并缺血性脑卒中的主要危险因素。其中经调整了其他危险因素的影响后,β2-AR-AA基因型、ACE-DD基因型相对危险度(OR)值分别为1.854(95%CI:1.041-3.301,P=0.036)和1.590(95%CI:1.019-2.481,P=0.041)。
结论:携带有β2-AR-AA基因型、ACE-DD基因型可能是高血压病合并缺血性脑卒中的独立危险因素。
Objective: To investigate the association between polymorphisms of the -1023 region ofβ2-adrenoceptor(β2-AR/-1023) gene-G/A,angiotensin converting enzyme (ACE) gene insertion/deletion(I/D) and essential hypertension(EH) complicated by ischemic cerebrovascular disease(ICVD).
Methods: We collected 345 subjects of EH-ICVD group, 315 subjects of EH without ICVD(EH-non-ICVD) group and 255 subjects of control group.β2-AR/-1023 gene-G/A were determined with the use of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP) methods,ACE gene-I/D polymorphisms were determined with the use of PCR,and polymorphic frequencies were compared in patients with EH-ICVD,EH-non-ICVD group and control. Information about prior exposure to various potential risk factors was also obtained. Chi-square test was used to compare difference of genotypes distribution among the three groups. The Hardy-Weinberg equilibrium was tested by Chi-square test of goodness of fit. Odds ratios for these comparisons of dangerous factors were calculated by Binary and Multinomial Logistic Regression.
Results: 1. The frequencies of different geneotypes ofβ2-AR/-1023 and ACE were in agreement with Hardy-Weinberg equilibrium in our study(P>0.05).
2. Chi-square test showed significant difference forβ2-AR-AA, AG and GG genotypes distribution in the three groups(χ2=11.834,P=0.019), and then Partitions ofχ2 method indicated thatβ2-AR-AA genotype frequencies in EH-ICVD group ( 12.5% ) were significantly higher than those in EH-non-ICVD group(7.0%)and Control group(5.5%) (χ2=10.298,P=0.001). The constituent ratio of ACE-II, ID, DD genotype was significantly different in the three groups(χ2=16.884,P=0.002), and then Partitions ofχ2 method showed that ACE–DD genotype frequencies in EH-ICVD group(20.9%) were significantly higher than those in EH-non-ICVD group(14.6%)and Control group(9.4%)(χ2=12.093,P=0.001). The 2 gene conjoint Analysis indicated significant difference of combined genotype frequencies in the three groups (χ2=27.814,P<0.001), furthermore, and Partitions ofχ2 method showed that AG/GG+II/ID combined genotype frequencies in EH-ICVD group(68.4%) were significantly lower than those in EH-non-ICVD group(79.7%)and Control group(85.9%)(χ2=24.073,P<0.001).
3. Multinomial Logistic-regression Analysis indicated that Smoke,Cholesterol, Blood Pressure Level,Blood Pressure Period,β2-AR-AA genotype,ACE-DD genotype were risk factors for EH-ICVD.The odds ratios(OR) of theβ2-AR-AA genotype vs AG/GG and ACE-DD genotype vs II/ID for EH-ICVD were 1.854 (95%CI:1.041-3.301,P=0.036) and 1.590 (95%CI:1.019-2.481, P=0.041) after adjusting other confounding factors, respectively.
Conclusion:β2-AR-AA and ACE-DD genotype may be the independent risk factors of hypertensive patients with ischemic cerebrovascular disease.
引文
1 李忠.缺血性脑血管疾病[M].北京:北京科学技术出版社,2002:1.
2 Bonita R. Epidemiology of stroke[J]. Lancet,1992,339(8789):342-344.
3 王 文 志 . 应 高 度 重 视 和 加 强 对 脑 卒 中 的 一 级 预 防 [J]. 中 国 现 代 神 经 疾 病 杂志,2006,6(1):1-2.
4 张林峰,杨军,武阳丰,等.我国人群中缺血性和出血性脑卒中发病的相对比例[J].中华内科杂志,2003,42(2):94-97.
5 朱 鼎 良 . 我 国 高 血 压 基 因 研 究 十 年 回 顾 和 几 点 建 议 [J]. 中 华 心 血 管 病 杂志,2005,33(7):585-587.
6 Rigat B, Hubert C, Corvol P,et al. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene(DCP1)[J]. Nucleic Acids Res, 1992, 20(6):1433.
7 J.萨姆布鲁克,D.W.拉塞尔主编.分子克隆实验指南(第三版)[M].北京:科学出版社,2002:390.
8 Kobilka BK, Frielle T, Collins S, et al. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins[J]. Nature,1987,329 (6134):75-79.
9 Munakata M. Beta 2-Adrenergic receptor gene polymorphisms[J]. Nippon Rinsho, 2001,59 (10):1889-1893.
10 Wu H,Cai GM,Xu HY,et al.Single nucleotide polymorphism in beta2-adrenoceptor gene and the distribution in Chinese Han ethnic group[J].Chin J Med Genet,2001, 18(1):123.
11 Alexandre C,Pereira,Marcilene S,et al.Beta2-adrenoceptor functional gene variants, obesity,and blood pressure level interactions in the general population[J]. Hypertension,2003,42 (2) :685-692.
12 Masuo K,Katsuya T,Fu Y,et al.Beta2- and beta3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years[J]. Circulation,2005,111(25):3429-3434.
13 Ranade K,Shue WH,Hung YJ,et al.The glycine allele of a glycine/arginine polymorphism in the Beta(2)-adrenergic receptor gene is association with essential Hypertension in apopulation of Chinese origin [J].AmJ Hypertention, 2001,14(12):1196-1200.
14 Li NF, Zhou L, Li T, Wang HM, et al.Association between the +491C/T polymorphism of beta2-adrenergic receptor gene and risk of essential hypertension in Kazakns of Xinjiang[J].Zhonghua Xin Xue Guan Bing Za Zhi, 2007,35(8):706-709.
15 Herrmann SM,Nicaud V ,Tiret L,et al . Polymorphism of the beta(2)-adrenergic receptor (ADRB2) gene and essential hypertension :the ECTIM and PEGASE studies[J]. Hypertension,2002,20(2):229-235.
16 Norihiro K,Takao S ,Hiroyuki M, et al.Association analysis of beta2-adrenergic receptor polymorphisms with hypertension in Japanese[J].Hypertension,2001, 37(1) :286-292.
17 Liang Y,Zhao YY,Liu H , et al . The genetype analysis of beta adrenergic receptor gene family in high risk population of hypertension in northeast China[J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi ,2004,21(2):124-127.
18 赵勇,马丽媛,王兴宇,等.β2-受体 Arg16Gly、Gln27Glu 多态性与缺血性脑卒中的关系[J].山东医药,2001,41(19):19-21.
19 Stanzione R, Di Angelantonio E, et al. Beta2-adrenergic receptor gene polymorphisms and risk of ischemic stroke[J]. Am J Hypertens.2007,20(6):657 -662.
20 Kobilka BK, Dixon RA, Frielle HG, et al. cDNA for the human β2-adrenergic receptor: a protein with multiple spanning domains and encoded by a gene whose chromosomal location is shared with that of a receptor for platelet growth factor[J]. Proc Natl Acad Sci USA ,1987, 84(1):46-50.
21 Castellano M, Bohm M. The cardiac beta-adrenoceptor-mediated signaling pathway and its alterations in hypertensive heart disease[J]. Hypertension,1997, 29(3):715-722.
22 Kume H, Hall LP, Washabau RJ, et al. Beta adrenergic agonists regulate KCa channels in airway smooth muscle by cAMP dependent and independent mechamisms[J]. J Clin Invest,1994,93(1): 371-379.
23 Daaka Y,Luttrill LM, Lefkowitz RJ. Switching of the coupling of the β2-adrenergic receptor to different G-proteins by protein kinase A[J].Nature,1997,390(6655): 88-91.
24 徐骏.β2 肾上腺素能受体激动对正常人血小板一氧化氮合酶活性的影响[J].东南大学学报(医学版),2002,21(4):306-307.
25 Collies S, Bouvier M, Bolanowslci MA, et al. Cyclic AMP stimulates transcription of theβ2-adrenergic receptor gene in response to shout term agonist exposure[J]. Proc Natl Acad Sci USA ,1989,86(13):4853-4857.
26 Mills PJ,Dimsdale JE,Ziegler MG,et al.Racial difference in epinephrine and β2-adrenergic receptors[J].Hypertension,1995,25(1):88-91.
27 谈红,张国元,黄超,等.冠心病、原发性高血压人群 ACE 基因多态性分布及序列测定[J].中华医学遗传学杂志,1999,16(3):145-148.
28 Tamaki S, Nakamura Y, Tsujita Y, et al. Polymorphism of the angiotensin converting enzyme gene and blood pressure in a Japanese general population (the Shigaraki Study) [J]. Hypertens Res,2002,25(6):843-848.
29 Gunes HV, Ata N, Degirmenci I,et al.Frequency of angiotensin-converting enzyme gene polymorphism in Turkish hypertensive patients[J].Int J Clin Pract, 2004,58(9):838-843.
30 Tiret L,Blanc H,Ruidavets JB et al.Gene polymorphisms of the rennin-angiotensin system in relation to hypertension and parental history of myocardial infarction and stroke: the PEGASE study[J]. J-Hypertens,1998;16(1):37-44.
31 吕冬霞,罗佳滨,朱金玲,等.ACE 基因 I/D 多态性与佳木斯地区汉族人群中老年原发性高血压的关系[J].中国老年学杂志,2005,25(5):531-532.
32 Di Pasquale P,Cannizzaro S,Scalzo S,et al.Cardiovascular effects of I/D angiotensin-converting enzyme gene polymorphism in healthy subjects.Findings after follow-up of six years[J]. Acta Cardiol,2005,60(4):427-435.
33 Ismail M,Akhtar N, Nasir M, et al.Association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and essential hypertension in young Pakistani patients[J].J Biochem Mol Biol,2004,37(5):552-555.
34 王芬,王束玫,吕明,等.血管紧张素转换酶基因插入/缺失多态性与维吾尔族人群高血压病的关系[J].中国动脉硬化杂志,2007,15(6):467-470.
35 姜玉,宋伟民.我国汉族人群血管紧张素转换酶基因多态性与原发性高血压关系的Meta 分析[J].环境与职业医学,2007,24(1):25-27,31.
36 Markus,Barley,Lunt,et al.Angiotensin-Converting Enzyme Gene Deletion Polymorphism:A New Risk Factor for Lacunar Stroke but not Carotid Atheroma [J].Stroke,1995,26(8):1329-1333.
37 吕晶,曲芳,王金华,等.血管紧张素转换酶基因多态性与急性脑血管病的关系[J].哈尔滨医药,2007,27(1):1-3.
38 呼日勒,牛广明,韩晓东,等.蒙古族腔隙性脑梗死患者的 ACE 基因多态性研究[J].卒中与神经病,2005,12(3):138- 139.
39 马晔,马建芳,陈喜军.ACE 基因多态性及其血浆水平与老年脑卒中的关系[J].东南国防医药,2007,9(1):21-23.
40 Karagiannis A, Balaska K, Tziomalos K,et al.Lack of an association between angiotensin-converting enzyme gene insertion /deletion polymorphism and ischaemic stroke[J].Eur Neurol,2004,51(3):148-52.
41 Dikmen M, Günes HV, Degirmenci I,et al.Are the angiotensin-converting enzyme gene and activity risk factors for stroke[J]?Arq Neuropsiquiatr,2006,64(2A): 211-6.
42 Sharma-P. Ischemic stroke and the gene for angiotensin-converting enzyme in Japanese hypertensives[J]. Circulation, 1997;95(1): 281-284.
43 Lin JJ,Yueh KC,Lin GY,et al.Lack of association between angiotensin I-converting enzyme gene deletion polymorphism and cerebrovascular disease in Taiwanese[J]. J Formos Med Assoc, 2000,99(12):895-901.
44 Um JY,Kim HM,Park HS,et al.Candidate genes of cerebral infarction and traditional classification in Koreans with cerebral infarction[J].Int J Neurosci,2005, 115(6):743-756.
45 莫照龙,卢锡林,陈飞,等.海南黎族缺血性脑卒中患者 ACE-1 基因多态性研究[J].中国热带医学,2006, 6(11):1947-1948.
46 Lindpaintne K, Lee M, Larson MG, et al. Absense of association or genetic linkage between the angiotensin-converting-enzyme gene and left ventricular mass[J]. N Engl J Med, 1996,334(16):1023-1028.
47 Hong SH,Kang BY,Park WH,et al. Genetic variation of the angiotensin-converting enzyme gene: increased frequency of the insertion allele in Korenans[J]. Clin Genet, 1997,51(1):35-38.
48 李才明,张成,卢锡林,等.血管紧张素转换酶基因与缺血性脑卒中发病的关系[J].中国危重病急救医学,2007,19(6):321-324.
49 Woods D, Sanders J, Jones A, et al. The serum angiotensin-converting enzyme and angiotensin II response to altered posture and acute exercise, and the influence of ACEgenotype[J]. Eur J Appi Physiol,2004,91(2-3):342-348.
50 Siragy H M,Carey R M. Angio tensin type-2 receptors: potential importance in the regulation of blood pressure[J]. Curr Opin Nephrol Hypertens,2001,10(1):99-103.
51 Romero JR, Reckelhoff JF. Role of angiotensin and oxidative stress in essential hypertension[J]. Hypertesion,1999, 34(part2):943-949.
52 Gaudet EA, Godwin SJ. Role of central catecholaminergic pathways in the actions of endogenous AngII on sympathetic reflexes[J].American Journal of physiology,1998,275(4pt2):1174-1184.
53 Ohira N,Matsumoto T,Tamaki S,et al.Angiotensin-converting enzyme insertion/ deletion polymorphism modulates coronary release of tissue plasminogen activator in response to bradykinin[J]. Hypertens Res,2004,27(1):39-45.
54 Kerins DM, Hao Q, Vaughan DE. Angiotensin induction of PAI-I expression in endothelial cells is mediated by the hexapeptide angiotensin IV[J]. J Clin Invest, 1995,96(5):2515-2520.
55 Kario k, Matsuo T, Kobayashi H, et al. Endothelial cell damage and angiotensin converting enzyme insertion/deletion genotype in elderly hypertention patients[J]. J Am Coll Cardiol, 1998,32(2):444-450.
56 Makris TK, Stavronlakis GA, Dafuni UG, et al. ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension[J]. Am Heart J, 2000,140(5):760-765.
57 Gonzalez Ordonez AJ, Fernandez Carreira JM, Medina Rodrignez JM, et al. Risk of venous thrombolism associated with the insertion/deletion polymorphism in the angiotensin-coverting enzyme gene[J].Blood Coagul Fibrinolysis,2000,11(5): 485-490.
58 Pezzini A,Grassi M,Zotto E,et al. Cumulative effect of predisposing genotypes and their interaction with modifiable factors on the risk of ischemic stroke in young adults[J]. Stroke,2005,36(3):533-539.
59 杨宇霞,孔祥东,吕宏宝,等.原发性高血压与血管紧张素转换酶基因及血管紧张素原基因多态性[J].河南医学研究,2002,11(2):109-111.
60 吴寿岭,郝冰,高竟生,等.血管紧张素转换酶基因多态性和血管紧张素Ⅱ受体-1 基因多态性与原发性高血压[J].高血压杂志,2003,11(1):38-41.
61 Clark CJ,Davies E,Anderson NH,et al.alpha-Adducin and angiotensin I-converting enzyme polymorphisms in essential hypertension[J].Hypertension,2000,36(6): 990-994.
62 赵利群,高平进,朱鼎良.ACE 基因和 adducin 基因联合作用与原发性高血压的关系[J].中国心血管病杂志,2006,11(1):16-19.
63 李才明,张成,卢锡林,等.缺血性脑卒中患者血管紧张素转换酶与 N5,N10-亚甲基四氢叶酸还原酶基因多态的关联性分析[J].中国医学科学院学报, 2007,29(3):359-363.
64 高旭光,霍阳,滕智平,等.四种基因多态性联合分析与脑梗死的关系研究[J].中华内科杂志,2005,44(12):933.
1 Rohrer DK. Physiological consequences of beta-adrenergic receptor disruption[J]. J Mol Med ,1998,76(11):764-772.
2 Kaumann AJ. Four beta-adrenoceptor subtypes in the mammalian heart[J]. Trends Pharmacol Sci,1997,18(3):70-76.
3 Johnson M.The beta-adrenoceptor[J].Am J Respir Crit Care Med,1998,158 (5Pt3): 146-153.
4 Kobilka BK,Dixon RA,Frielle HG,et al.cDNA for the human β2-adrenergic receptor:a protein with multiple spanning domains and encoded by a gene whose chromosomal location is shared with that of a receptor for platelet growth factor[J]. Proc Natl Acad Sci USA,1987,84(1):46-50.
5 Castellano M,Bohm M.The cardiac beta-adrenoceptor-mediated signaling pathway and its alterations in hypertensive heart disease[J]. Hypertension,1997, 29(3):715-722.
6 Strader CD,Sigal IS, Candelore MR, et al. Conserved aspartic acid residues 79 and 113 of the β-adrenergic receptor have different roles in receptor function[J]. J Biol Chem,1988,263(21): 10267-10271.
7 Strader CD, Candelore MR,Hill WS, et al. Identification of two serine residues involved in agonist activation of the β-adrenergic receptor[J]. J Biol Chem,1989,
264(23):13572-13580.
8 Totes MR, Candelore MR, Dixon RAF,et al.Biophysical and genetic analysis of the ligand45binding site of the beta-adrenoceptor[J]. Trends Pharmacol Sci ,1991,12(1):4-6.
9 Kume H, Hall LP, Washabau RJ, et al. Beta adrenergic agonists regulate KCa channels in airway smooth muscle by cAMP dependent and independent mechamisms[J]. J Clin Invest,1994,93(1): 371-379.
10 Daaka Y, Luttrill LM, Lefkowitz RJ. Switching of the coupling of the β2-adrenergic receptor to different G-proteins by protein kinase A[J]. Nature,1997, 390(6655): 88-91.
11 Collies S, Bouvier M, Bolanowslci MA, et al. Cyclic AMP stimulates transcription of the β2-adrenergic receptor gene in response to shout term agonist exposure[J]. Proc Natl Acad Sci USA ,1989,86(13): 4853-4857.
12 McGraw DW, Forties SL, Kramer, et al. Polymorphisms of the 5' leader cistron of the human beta2-adrenergic receptor regulate receptor expression[J]. J Clin Invest , 1998,102(11):1927-1932.
13 Hausdorff WP, Caron MG, Lefkowitz RJ. Turning off the signal: desensitization of β-adrenergic receptor function[J]. FASEB J ,1990,4(11):2881-2889.
14 Koch WJ, Rockman HA, Samama P, et al. Reciprocally altered cardiac functin in transgenic mice overexpressing the β-adrenergic receptor kinase or a βARK inhibitor[J]. Science,1995,268(5215):1350-1353.
15 Yang-Feng TL, Xue FY, Zhong WW, et al. Chromosomal organization of adrenergic receptor genes[J]. Proc Natl Acad Sci USA, 1990,87(4):1516-1520.
16 Kobilka BK, Frielle T, Collins S, et al. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins[J]. Nature,1987,329 (6134):75-79.
17 Munakata M. Beta 2-Adrenergic receptor gene polymorphisms[J]. Nippon Rinsho, 2001,59 (10):1889-1893.
18 吴宏,肖君华,蔡刚明,等.高血压病患者 β2-肾上腺素能受体基因 5′-调控区单核苷酸多态性研究[J].中华医学杂志,2001,81(1):23-26.
19 Kotanko P,Hoglinger O,Skrabal F.β2-adrenoceptor density in fibroblast culture correlates with human NaCl sensitirity[J]. Am J Physical,1992,263 (3pt):C623-627.
20 Lang CC,Teln CM,Brown RM,et al.Attenuation of isoproterenol-mediated v asodilation in blacks[J]. N Engl J Med,1995,333(3):155-160.
21 Gratze G, Fortin J , Labugger R, et al. Beta2-adrenergic receptor variants affect resting blood pessure and agonist-induced vasodilation in young adult caucasians[J]. Hypertension,1999,33 (6):1425-1430.
22 Hoit BD ,Suresh DP ,Craft L ,et al.β2-adrenergic receptor polymorphyisms at amino acid
16 differentially influence agonist-stimulated blood pressure and peripheral blood flow in normal individuals[J].America Heart Journal,2000,139(3): 537-542.
23 Dishy V,Sofowora GG,Xie H-G,Kim RB,et al.The effect of common polymorphisms of the β2-adrenergic receptor on agonist-mediated vascular desensitization[J]. N Engl J Med ,2001,345(14):1030-1035.
24 Stein CM ,Nelson R ,Deegan R , et al . Forearm β2 adrenergic receptor-mediated vasodilation is impaired ,without alteration of forearm norepinephrine spillover,in borderline hypertension[J].J Clin Invest,1995,96(1):579-585.
25 Skrabal F , Kotanko P ,Luft FC. Minireview:inverse regulation of α2 and β2 adrenoceptors in salt-sensitive hypertension:an hypothesis[J].Life Sci,1989,45(22): 2061-2076.
26 Busjahn A,Li GH,Faulhaber HD,et al.β2-adrenergic receptor gene variations, blood pressure,and heart size in normal twins[J].Hypertension,2000,35(2): 555-560.
27 Alexandre C,Pereira,Marcilene S,et al.Beta2-adrenoceptor functional gene variants,obesity,and blood pressure level interactions in the general population[J] . Hypertension,2003,42(2):685-692.
28 Sethi AA,Tybjaerg-Hansen A,Jensen GB,et al.164Ile allele in the beta2-Adrenergic receptor gene is associated with risk of elevated blood pressure in women,The Copenhagen City Heart Study[J].Pharmaco-genet Genomics,2005, 15(9):633-645.
29 Kotanko P,Binder A,Tasker J,et al.Essential hypertension in African Caribbeans associates with a variant of the beta2-adrenoceptor[J]. Hypertention,1997,30(4): 773 -776.
30 Wu H,Cai GM,Xu HY,et al.Single nucleotide polymorphism in beta2-adrenoceptor gene and the distribution in Chinese Han ethnic group[J].Chin J Med Genet ,2001, 18(1):123.
31 吴宏,宋秀峰,肖君华,等. 老年原发性高血压患者 β2-肾上腺素能受体基因两个单核苷酸多态性研究[J].中华医学遗传学杂志,2002,19(2):23-26.
32 Masuo K,Katsuya T,Fu Y,et al.Beta2- and beta3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years[J].Circulation,2005,111(25):3429-3434.
33 Ranade K,Shue WH,Hung YJ,et al.The glycine allele of a glycine/arginine polymorphism in the Beta(2)-adrenergic receptor gene is association with essential Hypertension in a population of Chinese origin[J].AmJ Hypertention, 2001,14(12):1196-1200.
34 Maciej T,Nick JR,Fadi J,et al.Essential hypertension and beta2-adrenergic receptor gene linkage and association analysis[J].Hypertension,2002,40(1): 286-291.
35 Herrmann SM,Nicaud V,Tiret L,et al.Polymorphism of the beta(2)-adrenergic receptor (ADRB2) gene and essential hypertension:the ECTIM and PEGASE studies[J]. Hypertension,2002,20(2):229-235.
36 Norihiro K,Takao S,Hiroyuki M, et al.Association analysis of beta2-adrenergic receptor polymorphisms with hypertension in Japanese[J].Hypertension,2001, 37(1):286-292.
37 Liang Y,Zhao YY,Liu H,et al.The genetype analysis of beta adrenergic receptor gene family in high risk population of hypertension in northeast China[J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi ,2004,21(2):124-127.
38 LoweMD, Rowland E, BrownMJ, et al. β2 adrenergic receptors mediate important electrophysiological effects in human ventricularmyocardium[J].Heart,2001,86(1): 45-51.
39. Billman GE, Castillo LC, Hensley J. et al. Beta2-adrenergic receptor antagonists protect against ventricular fibrillation: in vivo and in vitro evidence for enhanced sensitivity to beta2-adrenergic stimulation in animals susceptible to sudden death[J]. Circulation,1997,96(6):1914-1922.
40 ZhengM, Han QD, Xiao RP. Distinct β-adrenergic receptor subtype signicals in the heart and their pathophysiological relevance[J]. Acta Physiologica Sinica, 2004, 56(1): 1-15.
41 Abu-Amero K K,Al-Boudari O M,Mohamed G H,et al .The Glu27 genotypes of the Beta2-adrenergic receptors are predictors for severe coronary artery disease[J].BMC Medical Genetics, 2006,7(31):1471-2350.
42 Zee R Y,Cook N R, Reynolds R,et al.Haplotype analysis of the β2-adrenergic receptor gene and risk of myocardial infarction in humans[J].the Genetics society of America,2005,169(3):1583-1587.
43 Sotoodehia N,Siscovick D S,Vatta M,et al.β2-Adrenergic Receptor Genetic Variants and Risk of Sudden Cardiac Death[J].Circulation,2006,113(15): 1842-1848.
44 张萍,郭继鸿,王淑敏,等.β2-肾上腺素能受体单核苷酸多态性与心房颤动的相关性研究[J].中国实用内科杂志,2006,26(8):595-597.
45 Large V,Hellstrom L,Reynisdottir S,et al.Human β2-adrenoceptor gene polymorphisms are highly frequent in obesity and associates with altered adipocyte β2 adrenoceptor function[J].J Clin Invest,1997,100(12):3005-3013.
46 M.SCorbalan,A.Marti,L.Forga et al.β2-adrenergic receptor mutation and abdominal obesity risk:effect modification by gender and HDL-cholestrol[J].Eur J Nutr,2002 ,41(3):114-118.
47 焦谊,赵学信,张丽萍,等.β2-肾上腺素能受体基因 R16G 多态与哈萨克族男性肥胖的相关性[J].中华高血压杂志,2006,14(10):806-810.
48 李南方,骆秦,周玲,等. β2-肾上腺素能受体基因+46 位 Arg16/Gly 多态性与新疆哈萨克族 人 群 低 密 度 脂 蛋 白 胆 固 醇 水 平 的 关 系 [J]. 中 华 心 血 管 病 杂志,2005,33(12):1071-1074.
49 Ishiyama-Shigemoto S, Yamada K, Yuan X, et al. Association of polymorphisms in the beta2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetesmellitus[J]. Diabetologia, 1999,42(1):98-101.
50 Kim SH,Kim DJ,Seo IA,et al.significance of β2-adrenergic receptor polymorphism in obesity and type 2 diabetes mellitus in Korean subjects[J]. Metabolism, 2002,51(7):833-837.
51 骆秦,李南方,周玲,等.β2-肾上腺素能受体基因+46 位多态性与新疆哈萨克族人超重肥胖的关系[J].新疆医科大学学报,2005,28(1):8-11.
52 赵勇,马丽媛,王兴宇,等.β2-受体Arg16Gly、Gln27Glu多态性与缺血性脑卒中的关系[J].山东医药,2001,41(19):19-21.
2 Bonita R. Epidemiology of stroke[J]. Lancet,1992,339(8789):342-344.
3 王 文 志 . 应 高 度 重 视 和 加 强 对 脑 卒 中 的 一 级 预 防 [J]. 中 国 现 代 神 经 疾 病 杂志,2006,6(1):1-2.
4 张林峰,杨军,武阳丰,等.我国人群中缺血性和出血性脑卒中发病的相对比例[J].中华内科杂志,2003,42(2):94-97.
5 朱 鼎 良 . 我 国 高 血 压 基 因 研 究 十 年 回 顾 和 几 点 建 议 [J]. 中 华 心 血 管 病 杂志,2005,33(7):585-587.
6 Rigat B, Hubert C, Corvol P,et al. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene(DCP1)[J]. Nucleic Acids Res, 1992, 20(6):1433.
7 J.萨姆布鲁克,D.W.拉塞尔主编.分子克隆实验指南(第三版)[M].北京:科学出版社,2002:390.
8 Kobilka BK, Frielle T, Collins S, et al. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins[J]. Nature,1987,329 (6134):75-79.
9 Munakata M. Beta 2-Adrenergic receptor gene polymorphisms[J]. Nippon Rinsho, 2001,59 (10):1889-1893.
10 Wu H,Cai GM,Xu HY,et al.Single nucleotide polymorphism in beta2-adrenoceptor gene and the distribution in Chinese Han ethnic group[J].Chin J Med Genet,2001, 18(1):123.
11 Alexandre C,Pereira,Marcilene S,et al.Beta2-adrenoceptor functional gene variants, obesity,and blood pressure level interactions in the general population[J]. Hypertension,2003,42 (2) :685-692.
12 Masuo K,Katsuya T,Fu Y,et al.Beta2- and beta3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years[J]. Circulation,2005,111(25):3429-3434.
13 Ranade K,Shue WH,Hung YJ,et al.The glycine allele of a glycine/arginine polymorphism in the Beta(2)-adrenergic receptor gene is association with essential Hypertension in apopulation of Chinese origin [J].AmJ Hypertention, 2001,14(12):1196-1200.
14 Li NF, Zhou L, Li T, Wang HM, et al.Association between the +491C/T polymorphism of beta2-adrenergic receptor gene and risk of essential hypertension in Kazakns of Xinjiang[J].Zhonghua Xin Xue Guan Bing Za Zhi, 2007,35(8):706-709.
15 Herrmann SM,Nicaud V ,Tiret L,et al . Polymorphism of the beta(2)-adrenergic receptor (ADRB2) gene and essential hypertension :the ECTIM and PEGASE studies[J]. Hypertension,2002,20(2):229-235.
16 Norihiro K,Takao S ,Hiroyuki M, et al.Association analysis of beta2-adrenergic receptor polymorphisms with hypertension in Japanese[J].Hypertension,2001, 37(1) :286-292.
17 Liang Y,Zhao YY,Liu H , et al . The genetype analysis of beta adrenergic receptor gene family in high risk population of hypertension in northeast China[J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi ,2004,21(2):124-127.
18 赵勇,马丽媛,王兴宇,等.β2-受体 Arg16Gly、Gln27Glu 多态性与缺血性脑卒中的关系[J].山东医药,2001,41(19):19-21.
19 Stanzione R, Di Angelantonio E, et al. Beta2-adrenergic receptor gene polymorphisms and risk of ischemic stroke[J]. Am J Hypertens.2007,20(6):657 -662.
20 Kobilka BK, Dixon RA, Frielle HG, et al. cDNA for the human β2-adrenergic receptor: a protein with multiple spanning domains and encoded by a gene whose chromosomal location is shared with that of a receptor for platelet growth factor[J]. Proc Natl Acad Sci USA ,1987, 84(1):46-50.
21 Castellano M, Bohm M. The cardiac beta-adrenoceptor-mediated signaling pathway and its alterations in hypertensive heart disease[J]. Hypertension,1997, 29(3):715-722.
22 Kume H, Hall LP, Washabau RJ, et al. Beta adrenergic agonists regulate KCa channels in airway smooth muscle by cAMP dependent and independent mechamisms[J]. J Clin Invest,1994,93(1): 371-379.
23 Daaka Y,Luttrill LM, Lefkowitz RJ. Switching of the coupling of the β2-adrenergic receptor to different G-proteins by protein kinase A[J].Nature,1997,390(6655): 88-91.
24 徐骏.β2 肾上腺素能受体激动对正常人血小板一氧化氮合酶活性的影响[J].东南大学学报(医学版),2002,21(4):306-307.
25 Collies S, Bouvier M, Bolanowslci MA, et al. Cyclic AMP stimulates transcription of theβ2-adrenergic receptor gene in response to shout term agonist exposure[J]. Proc Natl Acad Sci USA ,1989,86(13):4853-4857.
26 Mills PJ,Dimsdale JE,Ziegler MG,et al.Racial difference in epinephrine and β2-adrenergic receptors[J].Hypertension,1995,25(1):88-91.
27 谈红,张国元,黄超,等.冠心病、原发性高血压人群 ACE 基因多态性分布及序列测定[J].中华医学遗传学杂志,1999,16(3):145-148.
28 Tamaki S, Nakamura Y, Tsujita Y, et al. Polymorphism of the angiotensin converting enzyme gene and blood pressure in a Japanese general population (the Shigaraki Study) [J]. Hypertens Res,2002,25(6):843-848.
29 Gunes HV, Ata N, Degirmenci I,et al.Frequency of angiotensin-converting enzyme gene polymorphism in Turkish hypertensive patients[J].Int J Clin Pract, 2004,58(9):838-843.
30 Tiret L,Blanc H,Ruidavets JB et al.Gene polymorphisms of the rennin-angiotensin system in relation to hypertension and parental history of myocardial infarction and stroke: the PEGASE study[J]. J-Hypertens,1998;16(1):37-44.
31 吕冬霞,罗佳滨,朱金玲,等.ACE 基因 I/D 多态性与佳木斯地区汉族人群中老年原发性高血压的关系[J].中国老年学杂志,2005,25(5):531-532.
32 Di Pasquale P,Cannizzaro S,Scalzo S,et al.Cardiovascular effects of I/D angiotensin-converting enzyme gene polymorphism in healthy subjects.Findings after follow-up of six years[J]. Acta Cardiol,2005,60(4):427-435.
33 Ismail M,Akhtar N, Nasir M, et al.Association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and essential hypertension in young Pakistani patients[J].J Biochem Mol Biol,2004,37(5):552-555.
34 王芬,王束玫,吕明,等.血管紧张素转换酶基因插入/缺失多态性与维吾尔族人群高血压病的关系[J].中国动脉硬化杂志,2007,15(6):467-470.
35 姜玉,宋伟民.我国汉族人群血管紧张素转换酶基因多态性与原发性高血压关系的Meta 分析[J].环境与职业医学,2007,24(1):25-27,31.
36 Markus,Barley,Lunt,et al.Angiotensin-Converting Enzyme Gene Deletion Polymorphism:A New Risk Factor for Lacunar Stroke but not Carotid Atheroma [J].Stroke,1995,26(8):1329-1333.
37 吕晶,曲芳,王金华,等.血管紧张素转换酶基因多态性与急性脑血管病的关系[J].哈尔滨医药,2007,27(1):1-3.
38 呼日勒,牛广明,韩晓东,等.蒙古族腔隙性脑梗死患者的 ACE 基因多态性研究[J].卒中与神经病,2005,12(3):138- 139.
39 马晔,马建芳,陈喜军.ACE 基因多态性及其血浆水平与老年脑卒中的关系[J].东南国防医药,2007,9(1):21-23.
40 Karagiannis A, Balaska K, Tziomalos K,et al.Lack of an association between angiotensin-converting enzyme gene insertion /deletion polymorphism and ischaemic stroke[J].Eur Neurol,2004,51(3):148-52.
41 Dikmen M, Günes HV, Degirmenci I,et al.Are the angiotensin-converting enzyme gene and activity risk factors for stroke[J]?Arq Neuropsiquiatr,2006,64(2A): 211-6.
42 Sharma-P. Ischemic stroke and the gene for angiotensin-converting enzyme in Japanese hypertensives[J]. Circulation, 1997;95(1): 281-284.
43 Lin JJ,Yueh KC,Lin GY,et al.Lack of association between angiotensin I-converting enzyme gene deletion polymorphism and cerebrovascular disease in Taiwanese[J]. J Formos Med Assoc, 2000,99(12):895-901.
44 Um JY,Kim HM,Park HS,et al.Candidate genes of cerebral infarction and traditional classification in Koreans with cerebral infarction[J].Int J Neurosci,2005, 115(6):743-756.
45 莫照龙,卢锡林,陈飞,等.海南黎族缺血性脑卒中患者 ACE-1 基因多态性研究[J].中国热带医学,2006, 6(11):1947-1948.
46 Lindpaintne K, Lee M, Larson MG, et al. Absense of association or genetic linkage between the angiotensin-converting-enzyme gene and left ventricular mass[J]. N Engl J Med, 1996,334(16):1023-1028.
47 Hong SH,Kang BY,Park WH,et al. Genetic variation of the angiotensin-converting enzyme gene: increased frequency of the insertion allele in Korenans[J]. Clin Genet, 1997,51(1):35-38.
48 李才明,张成,卢锡林,等.血管紧张素转换酶基因与缺血性脑卒中发病的关系[J].中国危重病急救医学,2007,19(6):321-324.
49 Woods D, Sanders J, Jones A, et al. The serum angiotensin-converting enzyme and angiotensin II response to altered posture and acute exercise, and the influence of ACEgenotype[J]. Eur J Appi Physiol,2004,91(2-3):342-348.
50 Siragy H M,Carey R M. Angio tensin type-2 receptors: potential importance in the regulation of blood pressure[J]. Curr Opin Nephrol Hypertens,2001,10(1):99-103.
51 Romero JR, Reckelhoff JF. Role of angiotensin and oxidative stress in essential hypertension[J]. Hypertesion,1999, 34(part2):943-949.
52 Gaudet EA, Godwin SJ. Role of central catecholaminergic pathways in the actions of endogenous AngII on sympathetic reflexes[J].American Journal of physiology,1998,275(4pt2):1174-1184.
53 Ohira N,Matsumoto T,Tamaki S,et al.Angiotensin-converting enzyme insertion/ deletion polymorphism modulates coronary release of tissue plasminogen activator in response to bradykinin[J]. Hypertens Res,2004,27(1):39-45.
54 Kerins DM, Hao Q, Vaughan DE. Angiotensin induction of PAI-I expression in endothelial cells is mediated by the hexapeptide angiotensin IV[J]. J Clin Invest, 1995,96(5):2515-2520.
55 Kario k, Matsuo T, Kobayashi H, et al. Endothelial cell damage and angiotensin converting enzyme insertion/deletion genotype in elderly hypertention patients[J]. J Am Coll Cardiol, 1998,32(2):444-450.
56 Makris TK, Stavronlakis GA, Dafuni UG, et al. ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension[J]. Am Heart J, 2000,140(5):760-765.
57 Gonzalez Ordonez AJ, Fernandez Carreira JM, Medina Rodrignez JM, et al. Risk of venous thrombolism associated with the insertion/deletion polymorphism in the angiotensin-coverting enzyme gene[J].Blood Coagul Fibrinolysis,2000,11(5): 485-490.
58 Pezzini A,Grassi M,Zotto E,et al. Cumulative effect of predisposing genotypes and their interaction with modifiable factors on the risk of ischemic stroke in young adults[J]. Stroke,2005,36(3):533-539.
59 杨宇霞,孔祥东,吕宏宝,等.原发性高血压与血管紧张素转换酶基因及血管紧张素原基因多态性[J].河南医学研究,2002,11(2):109-111.
60 吴寿岭,郝冰,高竟生,等.血管紧张素转换酶基因多态性和血管紧张素Ⅱ受体-1 基因多态性与原发性高血压[J].高血压杂志,2003,11(1):38-41.
61 Clark CJ,Davies E,Anderson NH,et al.alpha-Adducin and angiotensin I-converting enzyme polymorphisms in essential hypertension[J].Hypertension,2000,36(6): 990-994.
62 赵利群,高平进,朱鼎良.ACE 基因和 adducin 基因联合作用与原发性高血压的关系[J].中国心血管病杂志,2006,11(1):16-19.
63 李才明,张成,卢锡林,等.缺血性脑卒中患者血管紧张素转换酶与 N5,N10-亚甲基四氢叶酸还原酶基因多态的关联性分析[J].中国医学科学院学报, 2007,29(3):359-363.
64 高旭光,霍阳,滕智平,等.四种基因多态性联合分析与脑梗死的关系研究[J].中华内科杂志,2005,44(12):933.
1 Rohrer DK. Physiological consequences of beta-adrenergic receptor disruption[J]. J Mol Med ,1998,76(11):764-772.
2 Kaumann AJ. Four beta-adrenoceptor subtypes in the mammalian heart[J]. Trends Pharmacol Sci,1997,18(3):70-76.
3 Johnson M.The beta-adrenoceptor[J].Am J Respir Crit Care Med,1998,158 (5Pt3): 146-153.
4 Kobilka BK,Dixon RA,Frielle HG,et al.cDNA for the human β2-adrenergic receptor:a protein with multiple spanning domains and encoded by a gene whose chromosomal location is shared with that of a receptor for platelet growth factor[J]. Proc Natl Acad Sci USA,1987,84(1):46-50.
5 Castellano M,Bohm M.The cardiac beta-adrenoceptor-mediated signaling pathway and its alterations in hypertensive heart disease[J]. Hypertension,1997, 29(3):715-722.
6 Strader CD,Sigal IS, Candelore MR, et al. Conserved aspartic acid residues 79 and 113 of the β-adrenergic receptor have different roles in receptor function[J]. J Biol Chem,1988,263(21): 10267-10271.
7 Strader CD, Candelore MR,Hill WS, et al. Identification of two serine residues involved in agonist activation of the β-adrenergic receptor[J]. J Biol Chem,1989,
264(23):13572-13580.
8 Totes MR, Candelore MR, Dixon RAF,et al.Biophysical and genetic analysis of the ligand45binding site of the beta-adrenoceptor[J]. Trends Pharmacol Sci ,1991,12(1):4-6.
9 Kume H, Hall LP, Washabau RJ, et al. Beta adrenergic agonists regulate KCa channels in airway smooth muscle by cAMP dependent and independent mechamisms[J]. J Clin Invest,1994,93(1): 371-379.
10 Daaka Y, Luttrill LM, Lefkowitz RJ. Switching of the coupling of the β2-adrenergic receptor to different G-proteins by protein kinase A[J]. Nature,1997, 390(6655): 88-91.
11 Collies S, Bouvier M, Bolanowslci MA, et al. Cyclic AMP stimulates transcription of the β2-adrenergic receptor gene in response to shout term agonist exposure[J]. Proc Natl Acad Sci USA ,1989,86(13): 4853-4857.
12 McGraw DW, Forties SL, Kramer, et al. Polymorphisms of the 5' leader cistron of the human beta2-adrenergic receptor regulate receptor expression[J]. J Clin Invest , 1998,102(11):1927-1932.
13 Hausdorff WP, Caron MG, Lefkowitz RJ. Turning off the signal: desensitization of β-adrenergic receptor function[J]. FASEB J ,1990,4(11):2881-2889.
14 Koch WJ, Rockman HA, Samama P, et al. Reciprocally altered cardiac functin in transgenic mice overexpressing the β-adrenergic receptor kinase or a βARK inhibitor[J]. Science,1995,268(5215):1350-1353.
15 Yang-Feng TL, Xue FY, Zhong WW, et al. Chromosomal organization of adrenergic receptor genes[J]. Proc Natl Acad Sci USA, 1990,87(4):1516-1520.
16 Kobilka BK, Frielle T, Collins S, et al. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins[J]. Nature,1987,329 (6134):75-79.
17 Munakata M. Beta 2-Adrenergic receptor gene polymorphisms[J]. Nippon Rinsho, 2001,59 (10):1889-1893.
18 吴宏,肖君华,蔡刚明,等.高血压病患者 β2-肾上腺素能受体基因 5′-调控区单核苷酸多态性研究[J].中华医学杂志,2001,81(1):23-26.
19 Kotanko P,Hoglinger O,Skrabal F.β2-adrenoceptor density in fibroblast culture correlates with human NaCl sensitirity[J]. Am J Physical,1992,263 (3pt):C623-627.
20 Lang CC,Teln CM,Brown RM,et al.Attenuation of isoproterenol-mediated v asodilation in blacks[J]. N Engl J Med,1995,333(3):155-160.
21 Gratze G, Fortin J , Labugger R, et al. Beta2-adrenergic receptor variants affect resting blood pessure and agonist-induced vasodilation in young adult caucasians[J]. Hypertension,1999,33 (6):1425-1430.
22 Hoit BD ,Suresh DP ,Craft L ,et al.β2-adrenergic receptor polymorphyisms at amino acid
16 differentially influence agonist-stimulated blood pressure and peripheral blood flow in normal individuals[J].America Heart Journal,2000,139(3): 537-542.
23 Dishy V,Sofowora GG,Xie H-G,Kim RB,et al.The effect of common polymorphisms of the β2-adrenergic receptor on agonist-mediated vascular desensitization[J]. N Engl J Med ,2001,345(14):1030-1035.
24 Stein CM ,Nelson R ,Deegan R , et al . Forearm β2 adrenergic receptor-mediated vasodilation is impaired ,without alteration of forearm norepinephrine spillover,in borderline hypertension[J].J Clin Invest,1995,96(1):579-585.
25 Skrabal F , Kotanko P ,Luft FC. Minireview:inverse regulation of α2 and β2 adrenoceptors in salt-sensitive hypertension:an hypothesis[J].Life Sci,1989,45(22): 2061-2076.
26 Busjahn A,Li GH,Faulhaber HD,et al.β2-adrenergic receptor gene variations, blood pressure,and heart size in normal twins[J].Hypertension,2000,35(2): 555-560.
27 Alexandre C,Pereira,Marcilene S,et al.Beta2-adrenoceptor functional gene variants,obesity,and blood pressure level interactions in the general population[J] . Hypertension,2003,42(2):685-692.
28 Sethi AA,Tybjaerg-Hansen A,Jensen GB,et al.164Ile allele in the beta2-Adrenergic receptor gene is associated with risk of elevated blood pressure in women,The Copenhagen City Heart Study[J].Pharmaco-genet Genomics,2005, 15(9):633-645.
29 Kotanko P,Binder A,Tasker J,et al.Essential hypertension in African Caribbeans associates with a variant of the beta2-adrenoceptor[J]. Hypertention,1997,30(4): 773 -776.
30 Wu H,Cai GM,Xu HY,et al.Single nucleotide polymorphism in beta2-adrenoceptor gene and the distribution in Chinese Han ethnic group[J].Chin J Med Genet ,2001, 18(1):123.
31 吴宏,宋秀峰,肖君华,等. 老年原发性高血压患者 β2-肾上腺素能受体基因两个单核苷酸多态性研究[J].中华医学遗传学杂志,2002,19(2):23-26.
32 Masuo K,Katsuya T,Fu Y,et al.Beta2- and beta3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years[J].Circulation,2005,111(25):3429-3434.
33 Ranade K,Shue WH,Hung YJ,et al.The glycine allele of a glycine/arginine polymorphism in the Beta(2)-adrenergic receptor gene is association with essential Hypertension in a population of Chinese origin[J].AmJ Hypertention, 2001,14(12):1196-1200.
34 Maciej T,Nick JR,Fadi J,et al.Essential hypertension and beta2-adrenergic receptor gene linkage and association analysis[J].Hypertension,2002,40(1): 286-291.
35 Herrmann SM,Nicaud V,Tiret L,et al.Polymorphism of the beta(2)-adrenergic receptor (ADRB2) gene and essential hypertension:the ECTIM and PEGASE studies[J]. Hypertension,2002,20(2):229-235.
36 Norihiro K,Takao S,Hiroyuki M, et al.Association analysis of beta2-adrenergic receptor polymorphisms with hypertension in Japanese[J].Hypertension,2001, 37(1):286-292.
37 Liang Y,Zhao YY,Liu H,et al.The genetype analysis of beta adrenergic receptor gene family in high risk population of hypertension in northeast China[J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi ,2004,21(2):124-127.
38 LoweMD, Rowland E, BrownMJ, et al. β2 adrenergic receptors mediate important electrophysiological effects in human ventricularmyocardium[J].Heart,2001,86(1): 45-51.
39. Billman GE, Castillo LC, Hensley J. et al. Beta2-adrenergic receptor antagonists protect against ventricular fibrillation: in vivo and in vitro evidence for enhanced sensitivity to beta2-adrenergic stimulation in animals susceptible to sudden death[J]. Circulation,1997,96(6):1914-1922.
40 ZhengM, Han QD, Xiao RP. Distinct β-adrenergic receptor subtype signicals in the heart and their pathophysiological relevance[J]. Acta Physiologica Sinica, 2004, 56(1): 1-15.
41 Abu-Amero K K,Al-Boudari O M,Mohamed G H,et al .The Glu27 genotypes of the Beta2-adrenergic receptors are predictors for severe coronary artery disease[J].BMC Medical Genetics, 2006,7(31):1471-2350.
42 Zee R Y,Cook N R, Reynolds R,et al.Haplotype analysis of the β2-adrenergic receptor gene and risk of myocardial infarction in humans[J].the Genetics society of America,2005,169(3):1583-1587.
43 Sotoodehia N,Siscovick D S,Vatta M,et al.β2-Adrenergic Receptor Genetic Variants and Risk of Sudden Cardiac Death[J].Circulation,2006,113(15): 1842-1848.
44 张萍,郭继鸿,王淑敏,等.β2-肾上腺素能受体单核苷酸多态性与心房颤动的相关性研究[J].中国实用内科杂志,2006,26(8):595-597.
45 Large V,Hellstrom L,Reynisdottir S,et al.Human β2-adrenoceptor gene polymorphisms are highly frequent in obesity and associates with altered adipocyte β2 adrenoceptor function[J].J Clin Invest,1997,100(12):3005-3013.
46 M.SCorbalan,A.Marti,L.Forga et al.β2-adrenergic receptor mutation and abdominal obesity risk:effect modification by gender and HDL-cholestrol[J].Eur J Nutr,2002 ,41(3):114-118.
47 焦谊,赵学信,张丽萍,等.β2-肾上腺素能受体基因 R16G 多态与哈萨克族男性肥胖的相关性[J].中华高血压杂志,2006,14(10):806-810.
48 李南方,骆秦,周玲,等. β2-肾上腺素能受体基因+46 位 Arg16/Gly 多态性与新疆哈萨克族 人 群 低 密 度 脂 蛋 白 胆 固 醇 水 平 的 关 系 [J]. 中 华 心 血 管 病 杂志,2005,33(12):1071-1074.
49 Ishiyama-Shigemoto S, Yamada K, Yuan X, et al. Association of polymorphisms in the beta2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetesmellitus[J]. Diabetologia, 1999,42(1):98-101.
50 Kim SH,Kim DJ,Seo IA,et al.significance of β2-adrenergic receptor polymorphism in obesity and type 2 diabetes mellitus in Korean subjects[J]. Metabolism, 2002,51(7):833-837.
51 骆秦,李南方,周玲,等.β2-肾上腺素能受体基因+46 位多态性与新疆哈萨克族人超重肥胖的关系[J].新疆医科大学学报,2005,28(1):8-11.
52 赵勇,马丽媛,王兴宇,等.β2-受体Arg16Gly、Gln27Glu多态性与缺血性脑卒中的关系[J].山东医药,2001,41(19):19-21.
© 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 |