AT_(1)R基因3′-非翻译区A1166→C变异和CA重复序列多态性与藏族EH的关联分析  

Analyses on the association of CA repeat polymorphism and A1166→C variant in the 3′ flanking region of AT_(1)R gene with essential hypertension in Tibetans

作　　者：邱长春[1] 郑勇[1] 岑维浚[2] 朱席琳 刘英 崔超英 单广良[1] 卓玛次仁[2] 陈勇[2] 次旦罗布[2] 平措扎西[2] 庄兰平[2] 仁丹[2] 柴旦 格桑罗布[2] 刘怡雯[1] 乌正赉[1] 周文郁 

机构地区：[1]北京中国医学科学院中国协和医科大学基础医学研究所,100005 [2]西藏自治区人民医院 [3]西藏医学专科学校

出　　处：《中华医学遗传学杂志》2000年第6期381-385,共5页Chinese Journal of Medical Genetics

基　　金：美国中华医学基金会(CMB;96-657);国家自然科学基金(39760067和39870687)

摘　　要：目的　研究血管紧张素 的 型 (AT1 R)基因 3′-端 CA重复序列多态性和 A116 6→ C突变双等位标志是否与藏族原发性高血压 (essential hypertension,EH)的遗传易感性相关联。方法　以荧光标记 d CTP为底物 ,应用 PCR扩增和 ABI prism 377半自动测序及 PCR/ RFL P技术 ,通过病例 -对照研究、受累同胞对和家系连锁分析 ,鉴定 AT1 R基因 3′-端 CA重复序列多态性和 A116 6→ C点突变与藏族 EH的关联。结果　病例 -对照研究证明 ,AT1 R基因 3′-端 CA重复序列多态性与 EH相关联 ,χ2 =2 6 .44 ,P<0 .0 0 1,该位点杂合度为 0 .73,多态信息量为 0 .71。 AT1 R基因 3′-端 CA重复序列存在 11种等位基因 ,A7(138bp)为最常见等位基因 ,A8等位基因与 EH正相关 ,EH组和对照组中 A8等位基因频率分别为2 0 .5 %和 7.3% ,χ2 =9.6 4,P=0 .0 0 2 ,OR=3.46 ,95 % CI=1.44～ 8.5 1;受累同胞对 A8等位基因的共享连锁分析结果显示 ,χ2 =3.85 ,P=0 .0 2 5 ;家系连锁分析 L od score值为 0 .80 ,AT1 R基因 A116 6→C突变与EH无关 (P>0 .0 5 )。结论　 AT1 R基因 3′端 CA重复序列多态性与 EH相关 ,A8等位基因是藏族 EH的重要遗传标志 。Objective To investigate whether CA repeat polymorphism and A1166→C variant in the 3′ flanking region of AT 1R gene are in association with the genetic susceptibily to essential hypertension (EH) in Tibetans. Methods A case control study was carried out. Sibpair analysis and family linkage analysis were conducted. The CA repeat polymorphism of AT 1R gene was identified by polymerase chain reaction(PCR) with fluorescence labeled dCTP as substrate and by semi automatic sequence technology. The A1166→C variant was detected by PCR RFLP. Results Association of AT 1R gene locus with EH was confirmed through the case control study in a well characterized group of 113 Tibetan EH patients and 131 normotensives( χ 2 =26.44, P <0.001). A closer examination of this gene locus found 11 alleles from Tibetan population; allele A7 (138 bp) was more frequent in both the patients and the controls. Allele A8(140 bp) was in strong positive association with genetic susceptibility to EH in Tibetans. Frequency of allele A8 was 20.5% in EH and 7.3% in normotensives. The difference of allele frequencies between the groups was significant ( χ 2 =9.64, P =0.002, OR=3.46, 95% CI 1.44 8.51). Affected sibpair analysis showed χ 2=3.85, P =0.025; family linkage analysis gave Lod score of 0.80. No association between A1166→C variant in AT 1R gene and EH in Tibetans was observed( P >0.05). Conclusion The result suggests that CA repeat polymorphism of AT 1R gene be in association with EH in Tibetans, which implicates that AT 1R gene may be in linkage disequilibrium with the causative genes of EH.

关 键 词：原发性高血压 藏族 血管紧张素Ⅱ受体 受累同胞对 

分 类 号：R544.102[医药卫生—心血管疾病]