Stroke Research Today is a free monthly online journal that collates and summarizes the latest research about Stroke, including details on treatment, recovery, rehabilitation, signs, symptoms. | ||||||||
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Interaction of genetic risk factors confers higher risk for thrombotic stroke in male Chinese: a multicenter case-control study.Shen CD, Zhang WL, Sun K, Wang YB, Zhen YS, Hui RT Sino-German Laboratory for Molecular Medicine and Key Laboratory for Clinical Cardiovascular Genetics, FuWai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, P. R. China. Stroke is a polygenic or multifactorial disease, and each single susceptibility gene has modest effects. We hypothesize that combined effects of multiple genes might confer a higher stroke risk than a 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 for stroke. Plasma lipoprotein(a) [Lp(a)] level was defined as a categorical variable and also included. Interactions between genetic risk factors were detected by the multifactor dimensionality reduction (MDR) method and further evaluated by multivariate logistic regression analyses. A significant combined effect on stroke due to the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR), the T2354A polymorphism of 5-lipoxygenase activating protein (ALOX5AP), and Lp(a) level, was detected using the MDR method. Furthermore, the combination of MTHFR 677TT, ALOX5AP 2354AA and Lp(a) elevation (Lp(a) concentration > or = 30 mg/dL) was found to be strongly associated with thrombotic stroke in males (OR, 10.419; 95%CI, 2.602 to 41.749; P= 0.001) using the multivariate logistic regression model. In conclusion, our results show that a combination of genetic risk factors can confer a higher risk for stroke than a single risk factor, indicating that people with multiple genetic risk factors have a higher risk of stroke and should be targets for prevention of this disease. Published 24 July 2007 in Ann Hum Genet, 71: 620-9.
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