ASSOCIATION OF THE MISSENSE GLU298ASP VARIANT OF THE ENDOTHELIAL NITRIC-OXIDE SYNTHASE GENE WITH MYOCARDIAL-INFARCTION

Objectives. We examined the possible association between the missense Gln298Asp variant of the endothelial nitric oxide synthase (eNOS) gene and myocardial infarction (MI). Background. Endothelium-derived nitri c oxide (NO) plays a key role ire the regulation of vascular tone. Rec ently, 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 effect s by suppressing platelet aggregation, leukocyte adhesion anal smooth muscle cell proliferation. Methods. We screened 285 patients with an M I and 607 control subjects in Kumamoto Prefecture, Japan. Genotypes we re determined by polymerase chain reaction-restriction fragment-length polymorphism analysis. Results. The frequency of the missense Glu298A sp variant was significantly higher in the MI group than in the contro l 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 sh owed that the missense Glu298Asp variant was an independent risk facto r for MI, as was diabetes mellitus, hypertension, cigarette smoking, h ypercholesterolemia and body mass index. Conclusions. There was a sign ificant association of the mis-sense Glu298Asp variant of the eNOS gen e with MI. This marker-disease association may be doe to the impaired effects of NO on the cardiovascular system: dysregulation of vascular tone, platelet aggregation and leukocyte adhesion and smooth muscle ce ll proliferation, all of which promote coronary atherosclerosis and th rombosis. (C) 1998 by the American College of Cardiology.