Although metabolic syndrome has been recognized as a risk factor for ischemic stroke, genetic factors associated with ischemic stroke in individuals with metabolic syndrome remain unknown. We examined an association of genetic variants with ischemic stroke among individuals with or without metabolic syndrome. The study population comprised 4,387 unrelated Japanese individuals, including 1,884 individuals with metabolic syndrome (240 subjects with ischemic stroke and 1,644 controls) and 2,503 individuals without metabolic syndrome (280 subjects with ischemic stroke and 2,223 controls). The 150 polymorphisms examined in the present study were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). The initial chi-square test revealed that the C↷T polymorphism (rs9925481) of CLEC16A and the A↷G polymorphism (rs4923918) of SPTBN5 were significantly (P<0.005) associated with ischemic stroke among individuals with metabolic syndrome. No polymorphism was significantly associated with ischemic stroke among individuals without metabolic syndrome. Multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure revealed that the A↷G polymorphism (rs4923918) of SPTBN5 was significantly (P<0.005), and the C↷T polymorphism (rs9925481) of CLEC16A was almost significantly, associated with ischemic stroke in individuals with metabolic syndrome. Genetic variants that confer susceptibility to ischemic stroke may differ among individuals with or without metabolic syndrome. Stratification of subjects according to the presence or absence of metabolic syndrome may thus be important for personalized prevention of ischemic stroke based on genetic information.

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