Evidence for association of a common variant of the endothelial nitric oxide synthase gene (Glu(298)-> Asp polymorphism) to the presence, extent, and severity of coronary artery disease

Background: Genetic variants of endothelial nitric oxide synthase (eNOS) could influence individual
susceptibility to coronary artery disease.
Objective: To assess whether Glu298®Asp polymorphism of the eNOS gene is associated with the
occurrence and severity of angiographically defined coronary artery disease in the Italian population.
Methods: Polymerase chain reaction/restriction fragment length polymorphism analysis was done to
detect the Glu298®Asp variant of the eNOS gene in 201 patients with coronary artery disease and 114
controls. The severity of coronary artery disease was expressed by the number of affected vessels and
by the Duke scoring system.
Results: The frequencies of the eNOS Glu/Glu, Glu/Asp, and Asp/Asp genotypes in the coronary
artery disease group were significantly different from those of controls (45.3%, 38.8%, and 15.9% v
42.1%, 51.8%, and 6.1%, respectively; c2 = 8.589, p = 0.0136). In comparison with subjects who
had a Glu298 allele in the eNOS gene, the risk of coronary artery disease was increased among Asp/
Asp carriers (odds ratio 2.9, 95% confidence interval 1.2 to 6.8, p = 0.01) and was independent of
the other common risk factors (p = 0.04). There was a significant association between the eNOS
Glu298®Asp variant and both the number of stenosed vessels (mean (SEM), 2.3 (0.1) for Asp/Asp v 1.9
(0.1) and 1.8 (0.1) for Glu/Glu and Glu/Asp, respectively; p = 0.01) and the Duke score (56.1 (3.1)
for Asp/Asp v 46.7 (2.0) and 46.1 (1.9) for Glu/Glu and Glu/Asp, respectively; p = 0.02).
Conclusions: Glu298®Asp polymorphism of the eNOS gene appears to be associated with the presence,
extent, and severity of angiographically assessed coronary artery disease.