Association of variable number of tandem repeats in endothelial nitric oxide synthase gene with coronary artery disease

ABSTRACT

Endo-derived nitric oxide [NO] is synthesized from L-arginine by endothelium nitric oxide synthase [eNOS]. Since reduced NO synthesis has been implicated in the development of coronary atherosclerosis; we hypothesized that polymorphisms of NOS gene might be associated with increased susceptibility to this disorder and coronary artery disease [CAD]. We studied the 27 base pair tandem repeat polymorphism in intron4 of the endothelial nitric oxide synthase [eNOS] gene in 141 unrelated CAD patients with positive coronary angiograms in Shahid Rajaee Heart Hospital and 159 age matched control subjects without a history of symptomatic CAD. The study protocol was approved by the Iran University of Medical Sciences Ethics Committee. The eNOS gene intron4a/b VNTR polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels and other risk factors were also determined. The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 68.8, 29.1 and 2.1% in CAD subjects, and 81, 18.4 and 0.6% in control subjects, respectively. The genotype frequencies differed significantly between the two groups [X[2]=6.38 P=0.041]. The frequency of the allele was 16.7% in CAD subjects and 9.8% in control subjects and was significantly higher in the patients [X[2]=6.18 P=0.013, odds ratio=1.84]. Plasma lipids, except HDL-C were also remarkablely increased in CAD group