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Interaction of Genetic Risk Factors Confers Higher Risk for Thrombotic Stroke in Male Chinese: A Multicenter Case‐Control Study
Author(s) -
Shen ChunDuo,
Zhang WeiLi,
Sun Kai,
Wang YiBo,
Zhen YiSong,
Hui RuTai
Publication year - 2007
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2007.00364.x
Subject(s) - medicine , stroke risk , stroke (engine) , case control study , multicenter study , risk factor , control (management) , ischemic stroke , genetics , biology , randomized controlled trial , computer science , engineering , mechanical engineering , ischemia , artificial intelligence
Summary 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≥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.