Interaction between − 786TC polymorphism in the endothelial nitric oxide synthase gene and smoking for myocardial infarction in Korean population

BackgroundNitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) mediates endothelium-dependent vasodilation and antithrombotic action. Controversial results regarding the association of eNOS gene polymorphisms with myocardial infarction (MI) have been reported.MethodsA total of 932 individuals living in Seoul and the suburb, Korea, were randomly selected. Genomic DNA was prepared from blood leukocytes. A GT missense mutation in exon 7 (894GT) was screened using PCR-RFLP analysis. The genotypes of 3 mutations (− 786TC, − 922AG, and − 1468TA) in the 5′-flanking region were determined by a minisequencing protocol (SNaPshot), respectively.ResultsPair-wise linkage analysis revealed that 3 mutations of − 786TC, − 922AG, and − 1468TA were completely linked with each other (∣D′∣ = 1, r2 = 0.96–1.0). Furthermore, each of these mutant alleles (− 786C, − 922G, or − 1468A), but not 894T allele, was associated with the risk of MI. Multiple logistic regression analysis revealed that each of these mutant alleles was a predictive independent risk factor for the risk of MI (odds ratio, 1.69 for dominant effects, P < 0.05) after age and sex adjustments. Smoking further increased the odds ratio by 2.04 for the risk of MI when it was combined with the mutant alleles.ConclusionEach of 3 mutations (− 786TC, − 922AG, or − 1468TA) in the 5′-flanking region of eNOS gene may play a role in the pathogenesis of MI in Korean population, and also provides an evidence for a significant interaction between these mutations and smoking.