The Interaction Between eNOS and MTHFR Genetic Polymorphism Modify Effect of Cigarette Smoking on The Risk of Ischemic Stroke

Abstract

P-281 Introduction: Stroke has been related to a variety of risk factors including cigarette smoking which induce oxidative stress. Nitric oxide (NO) plays a relevant role in producing ROS and T-786C polymorphism in promoter region has been studied with various diseases. Methylenetetrahydrofolate reductase (MTHFR) gene may not be associated with disease outcome directly, the combination effect with other gene has been reported. We investigated the association between the eNOS T-786C and MTHFR C-677T genetic polymorphisms and the risk for stroke, and examined potential interaction between these polymorphisms and cigarette smoking. Methods: Total 290 cases arrived in emergency room within 24 hours after stroke and 290 age-sex matched controls were included in this study. SNP-IT was used for genotyping of eNOS and MTHFR gene. For analysis of association between these genetic polymorphisms and ischemic stroke, logistic regression was used. Results: The smoking was shown to increase the risk of stroke in the analysis controlling for polymorphisms and other significant variables, but the significant interaction between each polymorphism and smoking was not observed. When stratified by the eNOS and MTHFR genetic polymorphisms, the risky effect of smoking increased clearly. In the subjects with eNOS -786TT and MTHFR -677CC together, smokers had significantly increased OR compared to nonsmokers (OR, 3.83; 95% CI, 1.42, 10.27), and the interaction was observed (p=0.004). The increased risk of smoking also was shown in the subjects with eNOS -786 TC or CC and MTHFR -677 CT or TT, but it did not reach significance. Discussion and Conclusion: In conclusion, we found that smoking is a risk factor for ischemic stroke and the risk was modified when considering the combination effect of eNOS T-786C and MTHFR C-677T polymorphisms. Our findings suggest that there is gene-gene and gene-environment interaction between eNOS and MTHFR polymorphisms and smoking for the risk of stroke.