Association of genetic variants with myocardial infarction in Japanese individuals with or without metabolic syndrome

The etiology of metabolic syndrome (MetS) is highly complex, with both genetic and environmental factors being thought to play an important role. Although MetS has been recognized as a risk factor for myocardial infarction (MI), the genetic risk for MI in individuals with or without MetS has remained uncharacterized. We examined a possible association of genetic variants with MI in individuals with or without MetS separately. The study population comprised 4,424 individuals, including 1,918 individuals with MetS (903 subjects with MI and 1,015 controls) and 2,506 individuals without MetS (499 subjects with MI and 2,007 controls). The 150 polymorphisms examined in the present study were selected by genome-wide association studies of MI and ischemic stroke with the use of Affymetrix GeneChip Human Mapping 500K Array Set. Initial screening by the Chi-square test revealed that the C T polymorphism (rs1794429) of LRPAP1, the A -> G polymorphism (rs12373237) of LAMA3 and the A -> G polymorphism (rs3782257) of NCOR2 were significantly (false discovery rate of <0.05) associated with MI for individuals with MetS, and that the C -> G polymorphism (rs13051704) of TFF1 was significantly related to MI for individuals without MetS. Subsequent multivariable logistic analysis with adjustment for covariates revealed that rs1794429 of LRPAP1 (recessive model; P=0.0218; odds ratio=0.71) and rs3782257 of NCOR2 (dominant model; P=0.0057; odds ratio=1.94) were significantly associated with MI among individuals with MetS, and that rs13051704 of TFF1 (additive model; P=0.0100; odds ratio=0.55) was significantly associated with MI among individuals without MetS. The genetic variants that confer susceptibility to MI differ between individuals with or without MetS. Stratification of subjects according to the presence or absence of MetS may thus be important for personalized prevention of MI based on genetic information.