Page Andrea, Reich Heather, Zhou Joyce, Lai Vesta, Cattran Daniel C, Scholey James W, Miller Judith A
CIHR New Emerging Team, 11EN-221, Toronto General Hospital, University Health Network, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
J Am Soc Nephrol. 2005 Oct;16(10):3053-60. doi: 10.1681/ASN.2004110905. Epub 2005 Aug 10.
Endothelial function is dependent on the generation of nitric oxide (NO) by the enzyme endothelial NO synthase (eNOS). One functional coding polymorphism of the eNOS gene (G894-->T) is associated with reduced enzyme activity, increased coronary heart disease, and the development of end-stage renal failure. Because gender and renin-angiotensin system activation also play key roles in the development of renal and cardiovascular disease and because NO plays a role in the response to angiotensin II (AngII), it was hypothesized that the eNOS gene G894-->T polymorphism would be a determinant of the systemic and renal vascular response to AngII. Fifty young, healthy, normotensive individuals who were on a controlled sodium and protein diet for 1 wk underwent assessment of BP and renal hemodynamic function at baseline and during AngII infusion (4 ng/kg per min for 45 min). Participants were genotyped for the eNOS gene G894-->T polymorphism and then segregated into groups on the basis of gender and genotype (GG versus GT/TT). Baseline values for renal blood flow, effective renal plasma flow, and GFR were lower in men with the T allele compared with men who were homozygous for the G allele (P = 0.03), but the polymorphism was not associated with renal hemodynamic function in women. The BP responses to AngII were similar in men and women regardless of genotype. Both multivariate linear regression and analysis of covariance (ANCOVA) revealed a relationship between gender and genotype. Men with the GT/TT genotype exhibited a significantly greater decrease in GFR (P = 0.04) in response to AngII than did those with the GG genotype. This association was not observed in women. The eNOS gene G894-->T polymorphism is a determinant of both baseline renal hemodynamic function and the hemodynamic response to AngII in men but not in women.
内皮功能依赖于内皮型一氧化氮合酶（eNOS）生成一氧化氮（NO）。eNOS基因的一种功能性编码多态性（G894→T）与酶活性降低、冠心病增加以及终末期肾衰竭的发生有关。由于性别和肾素-血管紧张素系统激活在肾脏和心血管疾病的发生中也起关键作用，且NO在对血管紧张素II（AngII）的反应中起作用，因此推测eNOS基因G894→T多态性将是全身和肾脏血管对AngII反应的一个决定因素。50名年轻、健康、血压正常且接受了1周钠和蛋白质摄入量控制饮食的个体，在基线时以及AngII输注期间（4 ng/kg每分钟，共45分钟）接受了血压和肾脏血流动力学功能评估。对参与者进行eNOS基因G894→T多态性基因分型，然后根据性别和基因型（GG与GT/TT）进行分组。与G等位基因纯合的男性相比，携带T等位基因的男性的肾血流量、有效肾血浆流量和肾小球滤过率（GFR）的基线值更低（P = 0.03），但该多态性与女性的肾脏血流动力学功能无关。无论基因型如何，男性和女性对AngII的血压反应相似。多变量线性回归和协方差分析（ANCOVA）均显示性别与基因型之间存在关联。与GG基因型的男性相比，携带GT/TT基因型的男性对AngII的反应中GFR显著降低（P = 0.04）。在女性中未观察到这种关联。eNOS基因G894→T多态性是男性基线肾脏血流动力学功能以及对AngII血流动力学反应的一个决定因素，而在女性中并非如此。
