title: Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction.
abstract: OBJECTIVE
  We examined the possible association between the missense Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene and myocardial infarction (MI).
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiology, Kumamoto University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimasaki
authors.forename: H
authors.initials: H
authors.lastname: Yasue
authors.forename: M
authors.initials: M
authors.lastname: Yoshimura
authors.forename: M
authors.initials: M
authors.lastname: Nakayama
authors.forename: K
authors.initials: K
authors.lastname: Kugiyama
authors.forename: H
authors.initials: H
authors.lastname: Ogawa
authors.forename: E
authors.initials: E
authors.lastname: Harada
authors.forename: T
authors.initials: T
authors.lastname: Masuda
authors.forename: W
authors.initials: W
authors.lastname: Koyama
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ogawa
authors.forename: K
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D004730:Endothelium, Vascular / Q000201:enzymology*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009203:Myocardial Infarction / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A