Joint effects of eNOS gene T-786C and ADH2 Arg47His polymorphisms on the risk of premature coronary artery disease.

Introduction: Both T-786C mutation in endothelial nitric oxide synthase (eNOS) gene and alcohol dehydrogenase (ADH) gene polymorphism such as ADH3 gamma1/gamma2 have been reportedly associated with coronary artery disease (CAD). Since ADH2 Arg47His polymorphism is common in Asian population, the aim of this present study was to assess the interaction between eNOS gene T-786C and ADH2 Arg47His polymorphisms on premature CAD risk.

Materials And Methods: Hospital-based case-control study was conducted with 167 premature CAD and 235 late-onset CAD patients. Polymerase chain reaction restriction fragment length polymorphism was used to detect the polymorphisms. Multivariate logistic regression model was performed to adjust the potential confounders and estimate odds ratios (ORs) with 95% confidence intervals (CIs). Synergy index (S) was the measure to assess the interaction as departure from additivity.

Results: After the adjustment for the potential confounders, and compared with the carriers of TT and Arg/Arg as the reference, the ORs with 95% CIs in parentheses of premature CAD were that 1.13 (0.19-6.59) for CT or CC and Arg/Arg carriers; 2.24 (0.77-6.49) for TT and Arg/His or His/His carriers; 4.18 (1.32-13.22) for CT or CC and Arg/His or His/His carriers, respectively. Based on those ORs, S was 2.32 (95% CI: 0.37-14.72).

Conclusions: The mutant genotypes of eNOS gene T-786C mutation and the fast form of ADH2 Arg47His polymorphism had an additive interaction on the risk of premature CAD in Chinese population. Further investigations with big sample size are necessary for confirming this additive interaction.