Background: Nitric 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. Methods: A 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. Results: Pair-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. Conclusion: Each 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.
- Endothelial nitric oxide synthase gene
- Myocardial infarction
ASJC Scopus subject areas
- Clinical Biochemistry
- Biochemistry, medical