Bilsborough William, Green Daniel J, Mamotte Cyril D S, van Bockxmeer Frank M, O'Driscoll Gerard J, Taylor Roger R
Department of Cardiothoracic Surgery, Royal Perth Hospital, GPO Box X2213, Perth 6847, WA, Australia.
Atherosclerosis. 2003 Jul;169(1):131-8. doi: 10.1016/s0021-9150(03)00147-3.
Nitric oxide-dependent vasodilation is impaired early in the pathogenesis of vascular disease. Both the 4ab polymorphism of endothelial nitric oxide synthase (eNOS) and elevated plasma homocysteine are putatively associated with coronary artery disease (CAD). Few studies have investigated the influence of either on endothelial function in normal subjects. We aimed to examine any effect of three eNOS gene polymorphisms and plasma levels of homocysteine, folate and lipids on vascular endothelial function in normal healthy subjects. Community subjects (n=60) were selected for their eNOS genotype. Largely NOz.-dependent, flow-mediated dilation (FMD) of the brachial artery and the response to glyceryl trinitrate (GTN) were measured. Neither FMD nor response to GTN in 4a allele carriers was significantly different from that of 4b homozygotes, (7.1+/-0.5 S.E.M. vs. 7.1+/-0.6%) and (18.9+/-1.2 vs. 18.9+/-0.9%), respectively. Responses were also independent of the other polymorphisms. FMD was significantly correlated with HDL-cholesterol (P=0.02). After accounting for serum folate, there was a significant inverse correlation between FMD and plasma homocysteine (P=0.03). In these normal community subjects, plasma homocysteine and HDL-cholesterol were predictors of FMD despite subjects being recruited without regard to these variables and despite normal plasma levels.
一氧化氮依赖性血管舒张在血管疾病发病早期就会受损。内皮型一氧化氮合酶（eNOS）的4ab多态性和血浆同型半胱氨酸水平升高都被认为与冠状动脉疾病（CAD）有关。很少有研究调查它们对正常受试者内皮功能的影响。我们旨在研究三种eNOS基因多态性以及同型半胱氨酸、叶酸和血脂水平对正常健康受试者血管内皮功能的影响。根据eNOS基因型选择社区受试者（n = 60）。测量了主要依赖一氧化氮的肱动脉血流介导的舒张功能（FMD）以及对硝酸甘油（GTN）的反应。4a等位基因携带者的FMD和对GTN的反应与4b纯合子相比均无显著差异，分别为（7.1±0.5标准误对7.1±0.6%）和（18.9±1.2对18.9±0.9%）。反应也与其他多态性无关。FMD与高密度脂蛋白胆固醇显著相关（P = 0.02）。在考虑血清叶酸后，FMD与血浆同型半胱氨酸之间存在显著的负相关（P = 0.03）。在这些正常社区受试者中，尽管招募受试者时未考虑这些变量且血浆水平正常，但血浆同型半胱氨酸和高密度脂蛋白胆固醇仍是FMD的预测指标。
