藏族原发性高血压的遗传学研究

Genetic basis of essential hypertension in Tibetan

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 。

Objective To explore the role genetic factor plays in the pathogenesis 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) μg·L -1·h -1 and (72.6±4.6) ng/L, all significantly higher than those in the controls [(1.59±0.11) μg·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, χ 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.