Lack of association between endothelial nitric oxide synthase gene polymorphisms and risk of premature coronary artery disease in the Greek population

Objective - Genetic polymorphisms in the gene for endothelial nitric oxide synthase have been considered as potential risk factors for the development of coronary artery disease in some populations. Methods - We studied two polymorphisms of the NOS3 gene, the VNTR in intron 4 (4VNTR) and the Glu298Asp polymorphism in exon 7, in relation to the existence of premature coronary artery disease and the occurrence of myocardial infarction. A total number of 370 individuals of the Greek population was examined by PCR-RFLP method. The patient group consisted of 209 subjects, aged less than 58 years presenting symptomatic coronary artery disease, documented by coronary angiography. Results - The frequencies for bb, ab and aa genotypes of 4VNTR polymorphism were 0.67, 0.29, 0.04, respectively, for the patient group and 0.73, 0.24, 0.03 for the control group. The frequencies for GG (Glu/Glu), GT (Glu/Asp),TT (Asp/Asp) of the Glu298Asp polymorphism were 0.52, 0.41, 0.07, respectively, in patients compared to 0.47, 0.46, 0.07, in control subjects. Statistical analysis indicated that there are no significant differences in the frequencies of the genotypes between patients and control subjects for both polymorphisms. The combined analysis of the two polymorphisms indicated no synergistic effect of the a and T alleles on coronary artery disease. Conclusions - We have found no evidence for association between the a allele of the 4VNTR polymorphism, or the T allele of Glu298Asp polymorphism and the risk for premature coronary artery disease or occurrence of myocardial infarction. Furthermore, no synergistic contribution of these polymorphisms to the development of premature coronary artery disease has been observed.