青海地区藏族、汉族HIF-2a基因单核苷酸多态性与胃癌易感性的相关性研究
|
摘要
目的探讨青海地区藏、汉族HIF-2α基因单核苷酸多态性与胃癌易感的相关性。方法收集青海省藏医院、青海大学附属肿瘤医院、青海省肿瘤医院就诊胃癌患者(长期居住于青海地区)藏族51例、汉族60例。使用外周血提取DNA。采用聚合酶链式反应(PCR)扩增,并使用测序法检测HIF-2α基因的3个位点,分别为rs6715787、13419896、7598371,同时行相关性分析。结果rs6715787、rs7598371的单核苷酸多态性(SNP)基因型分别为C/G、C/C、G/G,rs13419896的SNP基因型为A/G、G/G、A/A。两组基因型分布检验后符合Hardy-Weinberg平衡规律(P <0.05)。藏、汉族胃癌组rs13419896的A/G、G/G、A/A基因型频率分别为27.45%、29.41%,43.13%、45.00%,43.33%、11.67%,基因型频率分布两组差异有高度统计学意义(χ2=14.195,P <0.01),其等位基因差异有高度统计学意义(χ2=11.495,P <0.01)。藏族胃癌组等位基因A频率分布高于汉族胃癌组。藏、汉族胃癌组rs7598371的C/G、C/C、G/G基因型频率分别为29.42%、37.25%、33.33%,41.67%、5.00%、53.33%,两组的基因型频率分布差异有统计学意义(χ2=18.118,P <0.01),其等位基因差异有高度统计学意义(χ2=16.002,P <0.01),藏族胃癌组等位基因C频率分布高于汉族胃癌组。藏、汉族胃癌组rs6715787的C/G、C/C、G/G基因型频率分别为35.29%、41.18%,23.52%、51.67%,8.33%、40.00%。两组基因型频率分布差异有高度统计学意义(χ2=16.675,P <0.01),其等位基因差异有高度统计学意义(χ2=13.518,P <0.01),藏族胃癌组等位基因C频率分布明显高于汉族胃癌组。基因位点藏汉族胃癌患者表达不同,其中青海地区藏族人群胃癌患者携带C/C型的HIF-2α基因的rs6715787高表达,藏族人群胃癌患者携带C/C型的HIF-2α基因rs7598371高表达,汉族人群胃癌患者携带C/G型的HIF-2α基因rs6715787高表达,汉族人群胃癌患者携带G/G型的HIF-2α基因rs7598371高表达。结论HIF-2α基因rs7598371、rs6715787、rs13419896与青海地区藏汉族胃癌可能无相关性,但青海地区藏族胃癌、汉族胃癌HIF-2α基因单核苷酸多态性存在差异,基因位点藏汉族对照组、藏汉族胃癌患者表达不同,提示青海地区藏族胃癌、汉族胃癌患者的基因型不同,遗传基础可能不同。
Objective To explore relationship between single nucleotide polymorphism of HIF-2Αα gene and susceptibility to gastric cancer of Qinghai area Tibetan, Han nationality. Methods A total of 51 Tibetan and 60 Han nationality patients(long lived in Qinghai area) with gastric cancer were collected. DNA was extracted from peripheral blood.Polymerase chain reaction(PCR) was used to detect 3 sites of HIF-2α gene, namely rs6715787, 13419896 and7598371, and correlation analysis was performed. Results The SNP genotypes of rs6715787 and rs7598371 were C/G,C/C and G/G, respectively, and the SNP genotypes of rs13419896 were A/G, G/G and A/A. The genotype frequencies of A/G, G/G and A/A in rs13419896 of Tibetan and Han nationality groups were 27.45%, 29.41%, 43.13% and45.00%, 43.33%, 11.67%, respectively. The difference in genotype frequency distribution between the two groups was highly statistically significant(χ2= 13.518, P < 0.01), and the difference in allele was highly statistically significant(χ2= 14.195, P < 0.01). The allele difference was statistically significant(χ2= 11.495, P < 0.01). The frequency distribution of allele A in Tibetan gastric cancer group was higher than that in Han nationality gastric cancer group. The C/G, C/C, G/G genotype frequencies of rs7598371 in the Tibetan and Han nationality groups were 29.42%,37.25%, 33.33% and 41.67%, 5.00%, 53.33%, respectively. The difference of genotype frequency distribution between the two groups was highly statistically significant(χ2= 18.118, P < 0.01), and the allele differences were highly statistically significant(χ2= 16.002, P < 0.01). The frequency distribution of allele C in Tibetan nationality gastric cancer group was higher than that in Han nationality gastric cancer group. The genotype distribution of the two groups was consistent with Hardy-Weinberg equilibrium law(P < 0.05). The C/G, C/C, G/G genotype frequencies of rs6715787 in the Tibetan and Han nationality group were 35.29%, 41.18%, 23.52% and 51.67%, 8.33%, 40.00%, respectively. The frequency distribution of allele C in Tibetan nationality gastric cancer group was highly significantly Higher nationality than that in han gastric cancer group(χ2= 16.675, P < 0.01). The expression of the gene loci was different in the Tibetan and Han nationality patients with gastric cancer, among which the high expression of HIF-2α gene of C/C type in the gastric cancer patients of Tibetan population in Qinghai province was found in rs6715787. The HIF-2α gene rs7598371 of C/C type was highly expressed in Tibetan gastric cancer patients. HIF-2α gene rs6715787 of C/G type is highly expressed in gastric cancer patients of Han nationality. The HIF-2α gene rs7598371 of G/G type was highly expressed in gastric cancer patients of Han nationality. Conclusion HIF-2α gene rs7598371, rs6715787, rs13419896 gastric cancer may be no correlation between the Han nationaltiy Chinese region of Qinghai Tibetan but region of Qinghai Tibetan, Han nationaltiy gastric cancer HIF-2α gene single nucleotide polymorphisms vary, gene loci to hide the control group, Tibetan and Han nationaltiy patients with gastric cancer express different, tip region of Qinghai Tibetan,Han nationaltiy gastric cancer patients with different genotypes, genetic basis may be different.
Objective To explore relationship between single nucleotide polymorphism of HIF-2Αα gene and susceptibility to gastric cancer of Qinghai area Tibetan, Han nationality. Methods A total of 51 Tibetan and 60 Han nationality patients(long lived in Qinghai area) with gastric cancer were collected. DNA was extracted from peripheral blood.Polymerase chain reaction(PCR) was used to detect 3 sites of HIF-2α gene, namely rs6715787, 13419896 and7598371, and correlation analysis was performed. Results The SNP genotypes of rs6715787 and rs7598371 were C/G,C/C and G/G, respectively, and the SNP genotypes of rs13419896 were A/G, G/G and A/A. The genotype frequencies of A/G, G/G and A/A in rs13419896 of Tibetan and Han nationality groups were 27.45%, 29.41%, 43.13% and45.00%, 43.33%, 11.67%, respectively. The difference in genotype frequency distribution between the two groups was highly statistically significant(χ2= 13.518, P < 0.01), and the difference in allele was highly statistically significant(χ2= 14.195, P < 0.01). The allele difference was statistically significant(χ2= 11.495, P < 0.01). The frequency distribution of allele A in Tibetan gastric cancer group was higher than that in Han nationality gastric cancer group. The C/G, C/C, G/G genotype frequencies of rs7598371 in the Tibetan and Han nationality groups were 29.42%,37.25%, 33.33% and 41.67%, 5.00%, 53.33%, respectively. The difference of genotype frequency distribution between the two groups was highly statistically significant(χ2= 18.118, P < 0.01), and the allele differences were highly statistically significant(χ2= 16.002, P < 0.01). The frequency distribution of allele C in Tibetan nationality gastric cancer group was higher than that in Han nationality gastric cancer group. The genotype distribution of the two groups was consistent with Hardy-Weinberg equilibrium law(P < 0.05). The C/G, C/C, G/G genotype frequencies of rs6715787 in the Tibetan and Han nationality group were 35.29%, 41.18%, 23.52% and 51.67%, 8.33%, 40.00%, respectively. The frequency distribution of allele C in Tibetan nationality gastric cancer group was highly significantly Higher nationality than that in han gastric cancer group(χ2= 16.675, P < 0.01). The expression of the gene loci was different in the Tibetan and Han nationality patients with gastric cancer, among which the high expression of HIF-2α gene of C/C type in the gastric cancer patients of Tibetan population in Qinghai province was found in rs6715787. The HIF-2α gene rs7598371 of C/C type was highly expressed in Tibetan gastric cancer patients. HIF-2α gene rs6715787 of C/G type is highly expressed in gastric cancer patients of Han nationality. The HIF-2α gene rs7598371 of G/G type was highly expressed in gastric cancer patients of Han nationality. Conclusion HIF-2α gene rs7598371, rs6715787, rs13419896 gastric cancer may be no correlation between the Han nationaltiy Chinese region of Qinghai Tibetan but region of Qinghai Tibetan, Han nationaltiy gastric cancer HIF-2α gene single nucleotide polymorphisms vary, gene loci to hide the control group, Tibetan and Han nationaltiy patients with gastric cancer express different, tip region of Qinghai Tibetan,Han nationaltiy gastric cancer patients with different genotypes, genetic basis may be different.
引文
[1]马颖才,熊元治,杨卫红,等.青海省胃癌高发区幽门螺杆菌特异蛋白与胃癌的关系[J].临床荟萃,2004,19(6):329-330.
[2]赫捷,陈万青.2012中国肿瘤登记年报[M].北京:军事医学科学出版社,2012.
[3]武文娣,李克莉,郑景山,等.中国2011年疑似预防接种异常反应监测数据分析[J].中国疫苗和免疫,2013,19(2):97-109.
[4]刘科,朱敏侠,蔡鹏,等.HIF-1α和HIF-2α在高原藏族胃癌中的表达及意义[J].基础医学与临床,2015,30(6):619-622.
[5]李能莲,李光明,骆亚莉,等.HIF-1α和HIF-2α在胃癌中的表达及意义[J].基础医学与临床,2010,30(6):619-622.
[6]吴巨钢,姜波健.细胞周期中胃癌相关基因的研究进展[J].实用医学杂志,2007,23(22):3487-3489.
[7]Wu Q,Luo G,Yang Z,et al.miR-17-5p promotes proliferation by targeting SOCS6 in gastric cancer cells[J].Lett Febs Letters,2016,588(12):2055-2062.
[8]王瑞权,黄志芳,陈志梅,等.HIF-1a及LMP3在胃癌中的表达及意义[J].现代实用医学,2011,23(10):1183-1185.
[9]王红磊,王洪涛,赵鹏,等.IGF-ⅡHIF-1a及CD105在胃癌中的表达及意义[J].临床医学工程,2011,18(5):668-670.
[10]刘科,朱敏侠,蔡鹏,等.HIF-1a和HIF-2a在高原藏族胃癌中的表达及意义[J].中外医疗,2015,34(28):72-74.
[11]衡艳艳.HIF-2a在急性缺血/缺氧性肾损伤发病中的作用及其机制研究[D].上海:复旦大学,2011.
[12]李倩,杨欢,高超,等.HIF-1a和CXCR4在胃癌组织中的表达及意义[J].徐州医学院学报,2013,33(3):159-163.
[13]刘晓丽,刘科,朱敏侠,等.高原藏族胃癌患者缺氧诱导因子-1a及缺氧诱导因子-2a表达水平及其作用机制的研究[J].中国现代医学杂志,2015,25(30):23-27.
[14]李强,陈志刚,王晓雷,等.HIF-2a在胃癌组织中的表达及肿瘤细胞凋亡的关系[J].河北医药,2013,35(15):2250-2252.(下转第22页)
[15]云芬,贾永峰,韩昭,等.非小细胞肺癌组织HIF-2a表达临床意义研究[J].中华肿瘤防治杂志,2016,23(13):860-865.
[16]谭浩,李广诚,朱宏,等.分子靶向与中医药治疗胃癌的研究进展[J].肿瘤药学,2017,7(2):135-139.
[17]冯波,王琦,武希润,等.维生素D及其类似物抗胃癌作用及机制的研究进展[J].肿瘤药学,2016,6(4):247-250.
[18]王莉,俞春江,耿敬姝,等.高原藏族胃癌患者缺氧诱导(上接第12页)因子-1a及VEGF在进展期胃癌中的表达及其意义[J].实用肿瘤学杂志,2005,19(5):337-340.
[19]Milne AN,Carneiro F,O′Morain C,et al.Nature meets nurture:molecular genetics of gastric cancer[J].Hum Genet,2009,126(5):615-628.
[20]王月,蔡哲,成建,等.替吉奥联合奥沙利铂治疗老年进展期胃癌的疗效[J].中国老年学杂志,2011,31(9):1504-1505.
[2]赫捷,陈万青.2012中国肿瘤登记年报[M].北京:军事医学科学出版社,2012.
[3]武文娣,李克莉,郑景山,等.中国2011年疑似预防接种异常反应监测数据分析[J].中国疫苗和免疫,2013,19(2):97-109.
[4]刘科,朱敏侠,蔡鹏,等.HIF-1α和HIF-2α在高原藏族胃癌中的表达及意义[J].基础医学与临床,2015,30(6):619-622.
[5]李能莲,李光明,骆亚莉,等.HIF-1α和HIF-2α在胃癌中的表达及意义[J].基础医学与临床,2010,30(6):619-622.
[6]吴巨钢,姜波健.细胞周期中胃癌相关基因的研究进展[J].实用医学杂志,2007,23(22):3487-3489.
[7]Wu Q,Luo G,Yang Z,et al.miR-17-5p promotes proliferation by targeting SOCS6 in gastric cancer cells[J].Lett Febs Letters,2016,588(12):2055-2062.
[8]王瑞权,黄志芳,陈志梅,等.HIF-1a及LMP3在胃癌中的表达及意义[J].现代实用医学,2011,23(10):1183-1185.
[9]王红磊,王洪涛,赵鹏,等.IGF-ⅡHIF-1a及CD105在胃癌中的表达及意义[J].临床医学工程,2011,18(5):668-670.
[10]刘科,朱敏侠,蔡鹏,等.HIF-1a和HIF-2a在高原藏族胃癌中的表达及意义[J].中外医疗,2015,34(28):72-74.
[11]衡艳艳.HIF-2a在急性缺血/缺氧性肾损伤发病中的作用及其机制研究[D].上海:复旦大学,2011.
[12]李倩,杨欢,高超,等.HIF-1a和CXCR4在胃癌组织中的表达及意义[J].徐州医学院学报,2013,33(3):159-163.
[13]刘晓丽,刘科,朱敏侠,等.高原藏族胃癌患者缺氧诱导因子-1a及缺氧诱导因子-2a表达水平及其作用机制的研究[J].中国现代医学杂志,2015,25(30):23-27.
[14]李强,陈志刚,王晓雷,等.HIF-2a在胃癌组织中的表达及肿瘤细胞凋亡的关系[J].河北医药,2013,35(15):2250-2252.(下转第22页)
[15]云芬,贾永峰,韩昭,等.非小细胞肺癌组织HIF-2a表达临床意义研究[J].中华肿瘤防治杂志,2016,23(13):860-865.
[16]谭浩,李广诚,朱宏,等.分子靶向与中医药治疗胃癌的研究进展[J].肿瘤药学,2017,7(2):135-139.
[17]冯波,王琦,武希润,等.维生素D及其类似物抗胃癌作用及机制的研究进展[J].肿瘤药学,2016,6(4):247-250.
[18]王莉,俞春江,耿敬姝,等.高原藏族胃癌患者缺氧诱导(上接第12页)因子-1a及VEGF在进展期胃癌中的表达及其意义[J].实用肿瘤学杂志,2005,19(5):337-340.
[19]Milne AN,Carneiro F,O′Morain C,et al.Nature meets nurture:molecular genetics of gastric cancer[J].Hum Genet,2009,126(5):615-628.
[20]王月,蔡哲,成建,等.替吉奥联合奥沙利铂治疗老年进展期胃癌的疗效[J].中国老年学杂志,2011,31(9):1504-1505.