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G蛋白β(3)亚基基因(GNB3)825T等位基因与早期高血压患者肾灌注增强有关。

G-protein beta(3) subunit gene (GNB3) 825T allele is associated with enhanced renal perfusion in early hypertension.

作者信息

Zeltner R, Delles C, Schneider M, Siffert W, Schmieder R E

机构信息

Department of Medicine/Nephrology, University of Erlangen-Nürnberg (Germany).

出版信息

Hypertension. 2001 Mar;37(3):882-6. doi: 10.1161/01.hyp.37.3.882.

Abstract

The C825T polymorphism of the gene encoding the G-protein beta(3) subunit (GNB3) is associated with increased intracellular signal transduction and arterial hypertension. The aim of the study was to investigate the impact of this polymorphism on early adaptive processes of the left ventricle and renal hemodynamic changes in young normotensive to mildly hypertensive subjects. Ninety-five white male students with normal or mildly elevated blood pressure were genotyped for the GNB3 C825T polymorphism. In each participant, 24-hour ambulatory blood pressure, left ventricular structure and function (2D-guided M-mode echocardiography), renal plasma flow (para-aminohippurate clearance), glomerular filtration rate (inulin clearance), and 24-hour urinary sodium excretion were determined. The GNB3 825T allele was not associated with casual or ambulatory blood pressure, parameters of left ventricular structure or function, glomerular filtration, or 24-hour urinary sodium excretion. However, in T:-allele carriers (CT+TT), renal plasma flow was higher than in CC subjects (CT/TT: 659+/-96 versus CC: 614+/-91 mL/min, P:=0.019). ANOVA disclosed that renal plasma flow was independently influenced by both genotype and blood pressure, with hypertensives having a higher renal plasma flow than normotensive subjects. This was the fact irrespective of the criteria used for the definition of hypertension (World Health Organization or 24-hour ambulatory blood pressure criteria). The GNB3 825T variant is associated with increased renal perfusion in this study. Because early renal hemodynamic changes play a pivotal role in the pathogenesis of essential hypertension, our data suggest a relevance of increased G-protein activation in the pathogenesis of hypertension.

摘要

编码G蛋白β(3)亚基(GNB3)的基因的C825T多态性与细胞内信号转导增强及动脉高血压相关。本研究的目的是调查这种多态性对年轻血压正常至轻度高血压受试者左心室早期适应性过程和肾脏血流动力学变化的影响。对95名血压正常或轻度升高的白人男性学生进行GNB3 C825T多态性基因分型。测定每位参与者的24小时动态血压、左心室结构和功能(二维引导M型超声心动图)、肾血浆流量(对氨基马尿酸清除率)、肾小球滤过率(菊粉清除率)和24小时尿钠排泄量。GNB3 825T等位基因与偶测或动态血压、左心室结构或功能参数、肾小球滤过或24小时尿钠排泄均无关联。然而,在T等位基因携带者(CT+TT)中,肾血浆流量高于CC受试者(CT/TT:659±96 vs CC:614±91 mL/min,P=0.019)。方差分析显示,肾血浆流量受基因型和血压的独立影响,高血压患者的肾血浆流量高于血压正常者。无论采用何种高血压定义标准(世界卫生组织标准或24小时动态血压标准),均是如此。在本研究中,GNB3 825T变异与肾脏灌注增加相关。由于早期肾脏血流动力学变化在原发性高血压发病机制中起关键作用,我们的数据提示G蛋白激活增加在高血压发病机制中具有相关性。

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