Schunkert H, Hense H W, Döring A, Riegger G A, Siffert W
From the Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany.
Hypertension. 1998 Sep;32(3):510-3. doi: 10.1161/01.hyp.32.3.510.
Gi proteins mediate the intracellular effects of many vasoactive and proliferative stimuli. Recently such signaling was found to be enhanced in cultured cells of some hypertensive subjects. A polymorphism at position 825 (C-->T) of the G protein beta3 subunit gene (GNB3) was strictly related to this phenotype. The aim of the present investigation was to test the association between this polymorphism and blood pressure and plasma renin levels in humans. A population-based sample (n=608) was analyzed by questionnaire and characterized for blood pressure; plasma renin, prorenin, and aldosterone levels; and Gbeta3 C825T allele status. In individuals without antihypertensive medication (n=474; age range, 52 to 67 years), the polymorphism was mildly associated with diastolic blood pressure (CC: 88.6+/-0.3 mm Hg, n=218; versus CT: 90.1+/-0.7 mm Hg, n=209; versus TT: 91.8+/-1.7 mm Hg, n=47; P=0.02 for trend) but not with systolic blood pressure. Furthermore, the 825T allele was also significantly associated with lower renin and prorenin levels, whereas the aldosterone to renin ratio was elevated in these subjects. Significant associations between the 825T allele and diastolic blood pressure, plasma renin, and prorenin levels (inverse), and the aldosterone to renin ratio persisted after adjustment for age, gender, body mass index, and systolic blood pressure. Finally, when the entire sample was considered and an adjustment was made for covariates, the presence of arterial hypertension and the use of antihypertensive medication were both 1. 8-fold higher in the TT than in the CC genotype group (P<0.05 and P=0.06, respectively). This observation, if replicated in further studies, suggests a molecular mechanism that unifies a higher diastolic blood pressure, a lower renin level, and an elevated aldosterone to renin ratio, ie, a combination of features frequently found in patients with arterial hypertension.
G蛋白介导许多血管活性和增殖性刺激的细胞内效应。最近发现，在一些高血压患者的培养细胞中，这种信号传导增强。G蛋白β3亚基基因（GNB3）第825位（C→T）的多态性与该表型密切相关。本研究的目的是测试这种多态性与人类血压和血浆肾素水平之间的关联。通过问卷调查对一个基于人群的样本（n = 608）进行分析，并对血压、血浆肾素、前肾素和醛固酮水平以及Gβ3 C825T等位基因状态进行特征描述。在未服用抗高血压药物的个体（n = 474；年龄范围52至67岁）中，该多态性与舒张压轻度相关（CC：88.6±0.3 mmHg，n = 218；CT：90.1±0.7 mmHg，n = 209；TT：91.8±1.7 mmHg，n = 47；趋势P = 0.02），但与收缩压无关。此外，825T等位基因也与较低的肾素和前肾素水平显著相关，而这些受试者的醛固酮与肾素比值升高。在对年龄、性别、体重指数和收缩压进行调整后，825T等位基因与舒张压、血浆肾素和前肾素水平（呈负相关）以及醛固酮与肾素比值之间的显著关联仍然存在。最后，当考虑整个样本并对协变量进行调整时，TT基因型组中动脉高血压的发生率和抗高血压药物的使用均比CC基因型组高1.8倍（分别为P < 0.05和P = 0.06）。如果在进一步研究中得到重复验证，这一观察结果提示了一种分子机制，该机制将较高的舒张压、较低的肾素水平和升高的醛固酮与肾素比值统一起来，即动脉高血压患者中常见的一组特征组合。
