Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction.

Abstract

We examined the possible association between the missense Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene and myocardial infarction (MI). Endothelium-derived nitric oxide (NO) plays a key role in the regulation of vascular tone. Recently, we reported that a missense Glu298Asp variant in exon 7 of the eNOS gene is a possible genetic factor involved in the pathogenesis of coronary spasm. Endothelium-derived NO also has vasoprotective effects by suppressing platelet aggregation, leukocyte adhesion and smooth muscle cell proliferation. We screened 285 patients with an MI and 607 control subjects in Kumamoto Prefecture, Japan. Genotypes were determined by polymerase chain reaction-restriction fragment-length polymorphism analysis. The frequency of the missense Glu298Asp variant was significantly higher in the MI group than in the control group (21.1% vs. 13.3%, p = 0.003, odds ratio 1.73 for the dominant effect of the eNOS T allele). Multiple logistic regression analysis showed that the missense Glu298Asp variant was an independent risk factor for MI, as was diabetes mellitus, hypertension, cigarette smoking, hypercholesterolemia and body mass index. There was a significant association of the missense Glu298Asp variant of the eNOS gene with MI. This marker-disease association may be due to the impaired effects of NO on the cardiovascular system: dysregulation of vascular tone, platelet aggregation and leukocyte adhesion and smooth muscle cell proliferation, all of which promote coronary atherosclerosis and thrombosis.