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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 ,提示致病基因可能与其存在连锁不平衡
Objective To investigate whether the 3’-terminal CA repeat polymorphism of the AT1R gene and the allelic sign of A116 6 → C mutation are associated with the genetic predisposition of Tibetan people with essential hypertension (EH) Associated. Methods Using fluorescence-labeled d CTP as substrate, PCR amplification, ABI prism 377 semi-automatic sequencing and PCR / RFL P technique were used to identify the 3’-terminal CA of AT1 R gene by case-control study and linkage analysis of sibling pairs and pedigrees. Repeated Sequence Polymorphism and A116 6 → C Mutation and Tibetan EH. Results The case-control study showed that the 3’-terminal CA repeat polymorphism of AT1 R gene was associated with EH (χ2 = 26.44, P <0.001). The heterozygosity at this locus was 0.73, The amount of polymorphic information is 0.71. The AT1 R gene 3’-terminal CA repeats 11 alleles, A7 (138bp) is the most common allele, A8 allele and EH positive correlation EH group and the control group A8 allele frequencies were 2 0 .5% and 7.3% respectively, χ2 = 9.64, P = 0.002, OR = 3.46, 95% CI = 1.44 ~ 8.51. The shared linkage analysis of affected sibling to A8 allele showed that χ2 = 3.85, P = 0.025; Lod score of linkage analysis of family was 0.80; A116 6 → C mutation of AT1 R gene was not related to EH (P> 0.05). Conclusion The 3 ’CA repeat polymorphism of AT1 R gene is associated with EH. The A8 allele is an important genetic marker of Tibetan EH, suggesting that the causative gene may be linked to its existence in an unbalanced manner