Division of Hypertension and Nephrology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
Hypertens Res. 2011 Jun;34(6):740-6. doi: 10.1038/hr.2011.25. Epub 2011 Mar 31.
Regulator of G-protein signaling 2 (RGS2) is a key molecule in signal pathways of vasoactive peptides, such as angiotensin II and endothelin 1, and is believed to have an important role in the pathophysiology of atherosclerosis. We have previously reported that common polymorphisms of RGS2 are associated with hypertension in Japanese. In this study, we studied whether the three previously identified common polymorphisms of RGS2 (-638A>G, 1026T>A and 1891-1892delTC) could be implicated in carotid atherosclerosis in Japanese patients with hypertension (459 men and 382 woman) and in a Japanese general population (814 men and 956 woman). We assessed two criteria for carotid atherosclerosis: maximal intima-media thickness (M-IMT) and mean-IMT. When subjects with atherosclerotic lesions were defined as having mean-IMT≥1.0 mm, multivariate logistic regression analysis performed after adjusting for confounding factors showed a significant association of the three common polymorphisms, -638A>G (AA versus AG+GG: odds ratio (OR), 1.55; 95% confidence interval (CI), 1.105-2.185; P=0.0113 only for the general population), 1026T>A (TT versus TA+AA: OR, 1.42; 95% CI, 1.027-1.972; P=0.034 for hypertensive subjects and OR, 1.56; 95% CI, 1.129-2.151; P=0.0071 for the general population), and 1891-1892delTC (II versus ID+DD: OR, 1.44; 95% CI, 1.043-2.008; P=0.028 for hypertensive subjects, OR, 1.32; 95% CI 1.002-1.742; P=0.048 for the total general population and OR 1.59; 95% CI 1.155-2.207; P=0.0047 for the general population), with carotid atherosclerosis. When atherosclerosis was defined as M-IMT 1.0 mm, the values of M-IMT were also significantly different between the three genotypes in the three common polymorphisms. Taken together, these data suggest that genetic polymorphisms in RGS2 are associated with intima-media thickening of carotid artery in humans.
RGS2 是血管活性肽（如血管紧张素 II 和内皮素 1）信号通路中的关键分子，被认为在动脉粥样硬化的病理生理学中具有重要作用。我们之前报道过，RGS2 的常见多态性与日本人的高血压有关。在这项研究中，我们研究了先前鉴定的三个常见 RGS2 多态性（-638A>G、1026T>A 和 1891-1892delTC）是否与日本高血压患者（459 名男性和 382 名女性）和日本普通人群（814 名男性和 956 名女性）的颈动脉粥样硬化有关。我们评估了颈动脉粥样硬化的两个标准：最大内膜中层厚度（M-IMT）和平均内膜中层厚度。当将具有动脉粥样硬化病变的患者定义为平均内膜中层厚度≥1.0mm 时，在调整混杂因素后进行的多变量逻辑回归分析显示，三个常见多态性-638A>G（AA 与 AG+GG：比值比（OR），1.55；95%置信区间（CI），1.105-2.185；P=0.0113，仅针对普通人群）、1026T>A（TT 与 TA+AA：OR，1.42；95%CI，1.027-1.972；P=0.034 高血压患者和 OR，1.56；95%CI，1.129-2.151；P=0.0071 普通人群）和 1891-1892delTC（II 与 ID+DD：OR，1.44；95%CI，1.043-2.008；P=0.028 高血压患者，OR，1.32；95%CI 1.002-1.742；P=0.048 普通人群和 OR，1.59；95%CI，1.155-2.207；P=0.0047 普通人群）与颈动脉粥样硬化有关。当将动脉粥样硬化定义为 M-IMT≥1.0mm 时，三个常见多态性中三个基因型之间的 M-IMT 也存在显著差异。综上所述，这些数据表明，RGS2 的遗传多态性与人类颈动脉内膜中层增厚有关。
