Endothelial nitric oxide synthase gene polymorphism, homocysteine, cholesterol and vascular endothelial function

• Published in: Atherosclerosis Vol. 169; no. 1; pp. 131 - 138
• Main Authors: Bilsborough, William, Green, Daniel J., Mamotte, Cyril D.S., van Bockxmeer, Frank M., O'Driscoll, Gerard J., Taylor, Roger R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.07.2003; Elsevier
• Subjects: Adult; Alleles; Biological and medical sciences; Brachial Artery - diagnostic imaging; Brachial Artery - physiology; Cardiovascular system; Cholesterol - blood; Cholesterol, HDL - blood; Endothelial function; Endothelium, Vascular - physiology; Folic Acid - blood; Genotype; HDL-cholesterol; Homocysteine; Homocysteine - blood; Humans; Investigative techniques of hemodynamics; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Nitric Oxide - physiology; Nitric oxide synthase; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type III; Polymorphism, Genetic; Ultrasonography; Ultrasound; Vasodilation - physiology; Nitric oxide synthase; Endothelial function; Homocysteine; Ultrasound; HDL-cholesterol; Human; Regional blood flow; Thiol; Enzyme; Brachial artery; Lipids; Cholesterol; Folate; Nitric-oxide synthase; Endothelium; Sulfur containing aminoacid; Vasomotricity; Gene; Homocystein; Oxidoreductases; Hemodynamics; Vascular wall; Polymorphism
• ISSN: 0021-9150; 1879-1484
• 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 NO -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.