Interaction Studies Of Stroke Genetic Risk Factors

Stroke is a polygenic or multifactorial disease, each single susceptibility gene with modest effects. We hypothesized that combined effects of multiple genes might confer higher stroke risk than does single susceptibility gene. To test our hypothesis, we initially recruited 2000 stroke patients (44.3% thrombosis, 28.3% lacunar infarction and 27.4% intracerebral hemorrhage) and 2000 controls, and examined 6 polymorphisms in 5 candidate genes of stroke. Plasma lipoprotein(a) [Lp(a)] level was defined as a categorical variable and also included. Interactions of genetic risk factors were detected by the multifactor dimensionality reduction (MDR) method and further evaluated by multivariate logistic regression analyses. A significant combination effects on stroke between C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR), T2354A polymorphism of 5-1ipoxygenase activating protein (ALOX5AP) and Lp(a) level was detected by using MDR method. Furthermore, the combination of MTHFR 677TT, ALOX5AP 2354AA and Lp(a) elevation (Lp(a) concentration≥30 mg/dL) was strongly associated with thrombotic stroke in males (OR, 10.419; 95%CI, 2.602 to 41.749; P=0.001) by using the multivariate logistic regression model.In conclusion, our results show that combination of genetic risk factors can confer higher risk for stroke than single risk factor, indicating that people with multiple genetic risk factors have higher risk for stroke and are the target for prevention of the disease.