藏族原发性高血压的遗传学研究

目的　探讨遗传因素在藏族原发性高血压 (EH)发病中的作用 ,以及血管紧张素Ⅱ的惟一前体物血管紧张素原 (AGT)基因变异是否参与EH发病。方法　以藏族 35 3例EH患者和 317名正常血压对照者为对象进行病例 对照相关研究。根据相似家系结构的指示对照和指示病例 1∶1配比分析 ,按Falconer公式计算藏族EH的遗传度。以聚合酶链反应 (PCR)和PCR产物的限制性片段长度多态性分析方法 ,分析AGT基因M2 35T多态性和 5′调控区 6A→G变异与藏族EH遗传易感的相关性。结果　 (1)藏族EH先证者 (指示病例 )一级亲属受累率为 43.3% ,EH遗传度为 77.2 %± 13 3%。(2 )EH患者血浆肾素活性 (μg·L-1·h-1)为 1.95± 0 .11,血管紧张素Ⅱ水平 (ng/L)为 72 .6± 4.6 ,均明显高于对照组 (分别为 1.5 9± 0 .11和 5 1.7± 4.6 ,P <0 .0 5 )。 (3)EH组AGT基因 5′调控区 6G等位基因频率 (0 .36 )明显高于对照组 (0 .2 7) (χ2 =9.35 ,P <0 .0 1) ,并与血管紧张素Ⅱ水平呈弱相关 ,而M2 35T多态性与EH易感无明显相关 (P >0 .0 5 )。结论　遗传因素在藏族EH发病中起重要作用 ,AGT基因可能是其重要易感基因之一

Genetic basis of essential hypertension in Tibetan

OBJECTIVE: To explore the role genetic factor plays in the pathogenes is of essential hypertension (EH) among Tibetans and to investigate whether angiotensinogen (AGT) is involved in the pathogenesis of EH. METHODS: A case-control association study was conducted among 353 essential hypertensive subjects and 317 genealogic structure-matched normotensive controls, all of Tibetan nationality. The correlation between polymorphism of M235T and 6A-->G variant in AGT gene and EH susceptibility in Tibetans was examined by polymerase chain reaction ( PCR) and PCR/RFLP (restriction fragment lengths polymorphism) with AspI and BstN I,respectively. RESULTS: (1) The affection rate of EH among the first-degree relatives of Tibetan EH proband was 43.3%.The heritability of EH was 77.2% +/- 13.3% by Falconer method. (2) The plasma rennin activity and angiotensin II (AngII) level among the EH patients were (1.95 +/- 0.11) microgram .L(-1).h(-1) and (72.6 +/- 4.6) ng/L, all significantly higher than those in the controls (1. 59 +/- 0.11) microgram .L(-1).h(-1) and (51.7 +/- 4.6) ng/L, all P < 0.05].(3) The -6G allele frequency in the promoter of AGT gene was higher in EH group than in the control group (0.36 vs 0.27, kappa(2) = 9.35, P < 0.01). There was a weak association between -6A -->G variant and the plasma AngII level, and there was no significant difference in the genotype distribution and allele frequency of M235T variant between the hypertensive and normotensive groups (P > 0.05). CONCLUSION: Genetic factor plays an important role in the pathogenesis of essential hypertension and angiotensinogen gene might be one of the most key susceptibility genes for essential hypertension in Tibetan.