Abstract 1258: Association of the e-NOS E298D Polymorphism and the Risk of Myocardial Infarction in the Greek Population
Introduction: The E298D polymorphic variant of endothelial nitric oxide synthase (e-NOS) has been variably associated with myocardial infarction (MI) in different populations. Data relating to this variant are controversial also in Greece. Accordingly, we examined a possible association between the E298D polymorphism of the e-NOS gene and MI in a subgroup of the Greek population.
Methods: The study population consisted of 204 patients with a history of MI and 218 healthy control subjects without history or electrocardiogram suggestive of MI. All subjects were selected from the general population of the greater Athens area. Age, gender and BMI were not different between groups. From each participant genomic DNA was extracted from peripheral blood leukocytes. The e-NOS E298D polymorphism was determined by Real-Time Polymerase Chain Reaction (RT-PCR) with melting curve analysis of PCR products from acceptor and donor probes specific for the polymorphism.
Results: The frequencies of the E298D (GG, GT and TT) genotypes were present in 83 (40.7%), 94 (46.1%), 27 (13.2%) of the 204 patients with MI; and 108 (49.5%), 95 (43.6%), 15 (6.9%) of the 218 healthy control subjects, respectively. The risk for MI in E298D TT was 2.064 (95% confidence interval [CI], 1.064 to 4.005), p=0.0343 versus GG+GT and 2.342 (95% CI, 1.171 to 4.684), p=0.0169 versus GG. The risk for the T allele was 1.416 (95%CI, 1.060 to 1.892), p=0.0222 versus G allele. This risk was higher when the genetic factor was combined with other risk factors, such as age <60 years and cigarette smoking. Smoking increased the odds ratio (OR) to 3.873 (95% CI: 1.481–10.132, p=0.0040) for TT versus GG and to 3.161 (95% CI: 1.249–7.997, p=0.0192) for TT versus GG and GT combined, suggesting a significant interaction between smoking and e-NOS gene polymorphism for MI. However, no association between the variant 298D allele and risk of MI was observed in non-smokers (OR=1.133, 95% CI: 0.2894– 4.439, p=1.0000).
Conclusions: This study indicates that E298D polymorphism of the e-NOS gene probably increases the risk for MI in the Greek population, especially when combined with smoking, suggesting a gene-environment interaction.