Received on July 21, 2005
Accepted on October 25, 2005

Molecular Diagnostics and Genetics

Hyperhomocysteinemia, Endothelial Nitric Oxide Synthase Polymorphism, and Risk of Coronary Artery Disease

¹ Research Unit 03/UR/08-14, Faculty of Pharmacy, Monastir, Tunisia, and Department of Cardiology, CHU Fattouma Bourguiba, Monastir, Tunisia, and Department of Biochemistry, Hospital Saint-Joseph, Paris, France
² Department of Cardiology, CHU Fattouma Bourguiba, Monastir, Tunisia
³ Department of Biochemistry, Hospital Saint-Joseph, Paris, France
⁴ Department of Biochemistry and Toxicology, CHU Hached, Sousse, Tunisia
⁵ Research Unit 03/UR/08-14, Faculty of Pharmacy, Monastir, Tunisia
⁶ Department of Biochemistry, Hospital Saint-Joseph, Paris, France, and Department of Biochemistry and Toxicology, CHU Hached, Sousse, Tunisia, and Department of Clinical Biochemistry, François Rabelais University, Tours, France

^* To whom correspondence should be addressed. E-mail: m.kerkeni{at}belgique.com.

Background: Hyperhomocysteinemia is an independent, graded risk factor for coronary artery disease (CAD). The G894T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia and could influence individual susceptibility to CAD. The aims of this study were to investigate (a) the relationship of the eNOS G894T polymorphism with the presence and the severity of CAD, and (b) the possible relationship between hyperhomocysteinemia and the eNOS G894T variant for the risk of CAD severity in a Tunisian population.

Methods: We used PCR-with restriction fragment length polymorphism analysis to detect the G894T variant of the eNOS gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed by the number of affected vessels. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay.

Results: The frequencies of the eNOS GG, GT, and TT genotypes in the CAD group were significantly different from those of control group (45%, 44%, and 11% vs 60%, 35.8% and 4.2%, respectively; P = 0.035). There was no association between the eNOS G894T genotype frequencies and the number of stenosed vessels (P = 0.149). In the CAD group, the coexistence of both the 894 GT or TT genotypes and hyperhomocysteinemia led to an increased risk of CAD severity.

Conclusion: The G894T polymorphism of the eNOS gene is associated with the presence of CAD, and in conjunction with hyperhomocysteinemia, increased the risk of CAD severity in a Tunisian population.