血管紧张素原基因5′端核心启动子区(-6)A-G和(-20)A-C变异与哈萨克族人原发性高血压相关性分析  

The relationship between the variants in 5' upstream core promoter A(-6)G and A(-20)C of angiotensinogen gene and essential hypertension in Kazakans of Xinjiang

作　　者：李南方[1] 周玲[1] 吴卫东[2] 石岩[2] 王新玲[1] 王君[1] 李红建[3] 张德莲[1] 祖合热[1] 欧阳玮进[1] 布克丽[1] 周克明[1] 成秋艳[1] 努尔古丽[1] 朱登浩 

机构地区：[1]新疆自治区人民医院高血压研究所,乌鲁木齐830001 [2]新疆自治区人民医院皮肤科,乌鲁木齐830001 [3]新疆医科大学 [4]新疆福海县人民医院

出　　处：《中华医学遗传学杂志》2004年第1期23-28,共6页Chinese Journal of Medical Genetics

基　　金：国家 8 63科研项目 (国科生字 [2 0 0 0 ] 1 1 2号 ) ;国家自然科学基金 (30 2 60 0 38;30 2 4 0 0 4 5)~~

摘　　要：目的　研究血管紧张素源 (angiotensinogen,AGT)基因核心启动子区域 (- 6 ) A- G和 (- 2 0 )A- C位点变异与哈萨克族人原发性高血压相关关系。方法　采用经典的饱和酚 /氯仿抽提法提取哈萨克族正常人 74名和高血压患者 12 5例白细胞基因组 DNA,通过 PCR、单链构象多态性、限制性片段长度多态性和测序等技术 ,鉴定不同个体 AGT基因核心启动子区域 (- 6 )、(- 2 0 )位等位基因的类型 ,观察在高血压组和正常血压组不同基因型的分布和等位基因频率的差异。结果　 (1)哈萨克族人 AGT基因 - 16 4～ +73区域仅存在 (- 6 ) A- G、(- 2 0 ) A- C两种变异。(2 ) AGT基因 (- 6 )位点 AA、AG、GG基因型的频率在高血压组和正常血压组分别为 0 .39、0 .4 5、0 .16和 0 .4 9、0 .4 9、0 .0 2 ,两组之间差异存在显著性 (χ2 =8.5 6 ,P=0 .0 14 )。A、G等位基因频率分别为 0 .6 2、0 .38和 0 .73、0 .2 7,差异存在显著性 (χ2 =5 .35 ,P=0 .0 2 1)。(3) AGT基因 (- 2 0 )位点 AA、AC、CC基因型频率在高血压组和正常血压组分别为 0 .6 9、0 .2 6、0 .0 5和 0 .6 5、0 .32、0 .0 3,差异无显著性 (χ2 =2 .4 2 ,P=0 .30 ) ;A、C等位基因的频率分别为 0 .82、0 .18和 0 .82、0 .18,差异无显著性 (χ2 =0 ,P=0 .99)。(4)ObjectiveTo investigate whether the variants A(-6)G and A(-20)C of angiotensinogen( AGT ) gene are involved in the pathogenesis of essential hypertension in Kazakans. Methods This case-control study recruited 125 subjects with hypertension and 74 normotensive subjects from Kazakans of Xinjiang. Genomic DNA from leukocytes was analyzed for genetic variants A(-6)G and A(-20)C in 5′ upstream core promoter of AGT gene by polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), restriction fragment length polymorphism (RFLP) and automatic sequencing. Results(1)There were only A(-6)G and A(-20)C variants in the -164 to +73 region of Kazakans' AGT gene. (2) The distributions of genotypes AA, AG, GG at locus -6 of AGT gene showed significant difference between the hypertensive group (0.39, 0.45, 0.16) and the normotensive group (0.49, 0.49, 0.02; χ 2=8.56, P=0.014). There were evident differences in the frequencies of the -6A and the -6G allele of the two groups (0.62, 0.38 and 0.73, 0.27; χ 2=5.35, P=0.021 ). (3) No significant difference was observed in the distribution of genotypes AA, AC, CC at locus -20 of AGT gene between the hypertensive group (0.69, 0.26, 0.05) and the normotensive group (0.65, 0.32, 0.03; χ 2=2.42, P=0.30) . There was no distinct difference in the frequencies of the -20A allele and the -20C allele of the two groups (0.82, 0.18 and 0.82, 0.18; χ 2=0, P=0.99 ). (4) No significant difference was found at the levels of systolic and diastolic blood pressure between the groups corresponding to genotypes at the loci -6 and -20 of AGT gene. Conclusion The results suggest that the polymorphism of A(-6)G in 5′ upstream core promoter of the AGT gene may be involved in the pathogenesis of essential hypertension in Kazakans, while the A(-20)C variant may not play an important role in the etiology of essential hypertension in Kazakans.

关 键 词：血管紧张素原基因 核心启动子区 遗传多态性 原发性高血压 哈萨克人 

分 类 号：R544.1[医药卫生—心血管疾病]