Endothelial nitric oxide synthase gene is associated with vessel stenosis in Korean population

Background: Nitric oxide (NO) produced by endothelial NO synthase (eNOS) mediates endothelium-dependent vasodilation and antithrombotic action. Controversial results regarding the association of eNOS gene polymorphisms with vessel stenosis have been reported. Methods: Age- and sex-matched 932 individuals (656 subjects having 1-, 2-, and 3-stenosed vessels and 276 controls without stenosis) living in Seoul and surrounding suburbs were selected. A GT missense mutation in exon 7 (894GT) was screened using PCR-restriction fragment length polymorphism analysis. The genotypes of a 27-bp insertion/deletion in intron 4 (eNOS4b/a) and a TC mutation in promoter region of -786 (-786TC) were determined by the banding pattern on gel electrophoresis and a commercially available minisequencing protocol (SNaPshot), respectively. Results: The eNOS4a allele was highly linked to the -786C allele (r=0.93, P<0.0001) while there was no linkage between eNOS4a allele and 894T allele or between 894T allele and -786C allele. Furthermore, 894T allele, but not eNOS4a (-786C) allele, was associated with the presence, but not the number, of stenosed vessels (odds ratio=1.57 for dominant effect of the T allele, P<0.05, and 1.49 for additive effect, P<0.05). Multiple logistic regression analysis revealed that 894T allele and hypertension were predictive independent risk factors for the presence of vessel stenosis. Conclusion: Our data suggest that eNOS gene polymorphisms may play an important role in the pathogenesis of vessel stenosis in Korean population.