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

The C825T polymorphism of the gene encoding the G-protein beta (2) subunit (GNB3) is associated with increased intracellular signal transduction and a rterial hypertension. The aim of the study was to investigate the impact of this polymorphism on early adaptive processes of the left ventricle and re nal hemodynamic changes in young normotensive to mildly hypertensive subjec ts. Ninety-five white male students with normal or mildly elevated blood pr essure 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-aminohippurat e clearance), glomerular filtration rate (inulin clearance), and 24-hour ur inary sodium excretion were determined. The GNB3 825T allele was not associ ated with casual or ambulatory blood pressure, parameters of left ventricul ar structure or function, glomerular filtration, or 24-hour urinary sodium excretion. However, in T-allele carriers (CT+TT), renal plasma flow was hig her 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 b y both genotype and blood pressure, with hypertensives having a higher rena l plasma flow than normotensive subjects. This was the fact irrespective of the criteria used for the definition of hypertension (World Health Organiz ation 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 essent ial hypertension, our data suggest a relevance of increased G-protein activ ation in the pathogenesis of hypertension.