Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with coronary artery disease in Iran

Endo-derived nitric oxide (NO) is synthesized from L-arginine by endothelium nitric oxide synthase (eNOS) encoded by the NOS3 gene on chromosome7. Since reduced NO synthesis has been implicated in the development of coronary atherosclerosis; polymorphisms of NOS gene might be associated with increased susceptibility to this disorder and coronary artery disease (CAD). We therefore undertook this study to determine the association between the occurrence of CAD and eNOS4 b/a polymorphism in Iranian patients.

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 and 159 age matched control subjects without a history of symptomatic CAD. 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 per cent in CAD subjects, and 81, 18.4 and 0.6 per cent in control subjects, respectively. The genotype frequencies differed significantly (P<0.05) between the two groups. The frequency of the a allele was 16.7 per cent in CAD subjects and 9.8 per cent in control subjects and was significantly higher in the patients (P<0.05, Odds ratio=1.84). Plasma lipids, except HDL-C were also significantly increased in CAD group.

Though the genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a, also 'a' allele frequency differed significantly between the CAD patients and controls, this polymorphism was not an independent risk factor for the development of CAD in Iranian patients. Further studies with larger samples need to be done to confirm these findings.