Influence of endothelial nitric oxide synthase gene polymorphisms (-786T>C, 4a4b, 894G>T) in Korean patients with coronary artery disease.

摘要

INTRODUCTION: Endothelium-derived nitric oxide (NO) is synthesized from l-arginine by endothelial nitric oxide synthase (eNOS) encoded by the eNOS3 gene on chromosome 7. The effects of the eNOS polymorphisms with the risk of coronary artery disease are conflicting. In this study, we investigated the association of the eNOS genotypes with coronary artery disease in Koreans. MATERIALS AND METHODS: A case-control study was performed to evaluate the association between the eNOS -786T>C, 4a4b, or 894G>T polymorphism and coronary artery disease. 147 consecutive patients with coronary artery disease and 222 healthy controls were recruited. The genotypes of eNOS -786T>C and 894G>T polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism analysis. The genotypes of a 27 bp insertion/deletion in intron 4 (eNOS 4a4b) were determined by the banding pattern on gel electrophoresis. RESULTS: The eNOS -786T>C (odds ratio [OR]; 1.61, 95% confidence interval [CI]; 0.97-2.69), 894G>T (OR; 1.12, 95% CI; 0.65-1.92) and 4a4b (OR; 1.44, 95% CI; 0.87-2.39) polymorphisms were not an independent predisposition factor to coronary artery disease. However, a subgroup analysis adjusted with various cardiovascular risk factors confirmed positive association of the -786T>C polymorphism in CAD patients with hypertension and a smoking history and also a significant association of the intron 4 genotypes with a smoking history, but no significance has been found in the eNOS polymorphisms of 894G>T upon any risk adjustment. In this study we also found that the distribution of heterozygotes (-786TC, 894GT, and 4a4b) and variant homozygotes for the -786C, 894T, and intron 4a alleles of eNOS in Koreans were significantly lower than in Caucasian populations. CONCLUSIONS: The present study demonstrates that polymorphisms of the eNOS -786T>C and 4a4b are associated with coronary artery disease with adjustments for cardiovascular risk factors in the Koreans.