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

Bilsborough, William; Green, Daniel J.; Mamotte, Cyril D.S.; van Bockxmeer, Frank M.; O'Driscoll, Gerard J.; Taylor, Roger R.

doi:10.1016/S0021-9150(03)00147-3

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Volume 169, Issue 1 , Pages 131-138, July 2003

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

William Bilsborough
- Department of Cardiothoracic Surgery, Royal Perth Hospital, GPO Box X2213, Perth 6847, WA, Australia
- Department of Medicine, University of Western Australia, Perth, Australia
- West Australian Institute for Medical Research, Perth, Australia
- Corresponding author. Tel.: +61-8-9224-3443; fax: +61-8-9224-1464
Daniel J. Green
- Department of Human Movement and Exercise Science, University of Western Australia, Perth, Australia
- Department of Cardiology, Royal Perth Hospital, Perth, Australia
- West Australian Institute for Medical Research, Perth, Australia
Cyril D.S. Mamotte
- Department of Immunology, Royal Perth Hospital, Perth, Australia
- Department of Biochemistry, Royal Perth Hospital, Perth, Australia
- West Australian Institute for Medical Research, Perth, Australia
Frank M. van Bockxmeer
- Department of Biochemistry, Royal Perth Hospital, Perth, Australia
- Department of Pathology, University of Western Australia, Perth, Australia
- West Australian Institute for Medical Research, Perth, Australia
Gerard J. O'Driscoll
- Department of Cardiology, Royal Perth Hospital, Perth, Australia
- West Australian Institute for Medical Research, Perth, Australia
Roger R. Taylor
- Department of Medicine, University of Western Australia, Perth, Australia
- Department of Cardiology, Royal Perth Hospital, Perth, Australia
- West Australian Institute for Medical Research, Perth, Australia

Received 4 December 2002; received in revised form 14 March 2003; accepted 2 April 2003.

Abstract

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.