Endothelial nitric oxide synthase -786T>C, but not 894G>T and 4a4b, polymorphism influences plasma homocysteine concentrations in persons with normal vitamin status

Abstract

Background: Nitric oxide (NO) plays a relevant role in various events during atherogenesis. In vitro data suggest that NO may modulate homocysteine (Hcy) concentrations. The aim of this study was to investigate the role of endothelial nitric oxide synthase (eNOS) -786T>C, 894G>T, and 4a4b polymorphisms in influencing Hcy concentrations. Methods: Blood samples were obtained from 1287 unrelated persons. Plasma Hey was measured by fluorescence polarization immunoassay, folate and vitamin B12 by RIA, vitamin B6 by HPLC, and eNOS and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms by PCR with restriction fragment length polymorphism analysis. Results: MTHFR 677C>T polymorphism significantly influenced Hey concentrations after adjustment for all confounding variables (P <0.0001 for trend). Univariate analysis showed that the eNOS -786T>C polymorphism, but not 894G>T and 4a4b, was significantly associated with the risk of having Hey in the third tertile [>13.4 μmol/L; odds ratio (OR) = 1.2; 95% confidence interval (CI), 1.02-1.5; P = 0.03]. After adjustment for all variables known to influence Hey, the -786T>C polymorphism still influenced Hey concentrations (OR = 1.9; 95% CI, 1.1-3.2; P = 0.01). By analyzing the influence of eNOS polymorphisms on plasma Hey concentrations according to vitamin concentrations (folate, vitamin B6, and vitamin B12), age, and smoking habits, we found a significant association between the eNOS -786T>C polymorphism and Hey in nonsmokers, in persons with normal vitamin status, and in persons <60 years. Conclusion: The eNOS -786T>C polymorphism, but not 894G>T and 4a4b, influences plasma Hey concentrations mildly but significantly and independently. © 2005 American Association for Clinical Chemistry.