Association between Endothelial Nitric Oxide Synthase Polymorphisms and Risk of Metabolic Syndrome

BACKGROUND Previous studies inferring that the NOS3 gene was associated with the pathogenesis of metabolic syndrome (MetS) had inconsistent findings. We investigated the role of three NOS3 polymorphisms (T-786C, intron 4b/a, and G894T) in the risk of MetS using a hospital-based case-control study. METHODS We recruited 339 MetS cases and 783 non-MetS controls at a central Taiwanese hospital. Information on sociodemographic and lifestyle factors was obtained using a self-administered questionnaire. Genotypes of NOS3 polymorphisms were compared between cases and controls. Effects of interactions between gene polymorphisms and smoking and between gene polymorphisms and drinking on the risk of MetS were also determined. RESULTS The T-786C TC+CC genotype was significantly associated with a decreased risk of MetS (odds ratio (OR), 0.63; 95% confidence interval (CI), 0.43-0.91), compared to the T-786C TT genotype, according to a logistic regression analysis. This beneficial effect was much greater for those who had ever smoked cigarettes (OR, 0.47; 95% CI, 0.26-0.87) or those who had not consumed alcohol (OR, 0.45; 95% CI, 0.26-0.77). In addition, the intron 4b/a variant genotype was marginally associated with a reduced risk of MetS (OR, 0.68; 95% CI, 0.47-1.00), compared to the intron 4b/a bb genotype, particularly for never alcohol consumers (OR, 0.56; 95% CI, 0.33-0.95). In the haplotype analysis, there was a 53% decrease in the MetS risk among C4bG haplotype carriers (OR, 0.47; 95% CI, 0.25-0.90), compared to those with the most common T4bG haplotype. CONCLUSIONS Our results suggest that the NOS3 T-786C and intron 4b/a polymorphisms may contribute to the risk of MetS. Further studies are needed to confirm the findings.