Endothelial nitric oxide synthase gene polymorphism, homocysteine, cholesterol and vascular endothelial function.
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.
Bilsborough
William
W
Department of Cardiothoracic Surgery, Royal Perth Hospital, GPO Box X2213, Perth 6847, WA, Australia. bill.bilsborough@health.wa.gov.au
Green
Daniel J
DJ
Mamotte
Cyril D S
CD
van Bockxmeer
Frank M
FM
O'Driscoll
Gerard J
GJ
Taylor
Roger R
RR
D000328:Adult; D000483:Alleles; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000502:physiology; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology*; D005492:Folic Acid / Q000097:blood; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic; D014463:Ultrasonography; D014664:Vasodilation / Q000502:physiology*
D008076:Cholesterol, HDL; D006710:Homocysteine; D009569:Nitric Oxide; D005492:Folic Acid; D002784:Cholesterol; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III