Abstract 1897: Genetic Variants That Confer Susceptibility to Myocardial Infarction Differ Among Individuals With or Without Hypertension or Diabetes Mellitus
Introduction. Hypertension and diabetes mellitus are important risk factors for myocardial infarction (MI). Recent evidence suggests that genetic variants associated with MI may differ between men and women, and in the absence or presence of conventional risk factors for atherosclerosis.
Hypothesis. We assessed the hypothesis that genetic variants that confer susceptibility to MI might differ among individuals with or without hypertension or diabetes mellitus.
Methods. The study population comprised 5835 unrelated Japanese individuals (3309 men, 2526 women), including 1339 subjects with MI (1048 men, 291 women) and 4496 controls (2261 men, 2235 women). The 150 polymorphisms examined in the present study were selected by genome-wide association studies of MI and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix).
Results and Conclusions. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that three different polymorphisms were significantly (P < 0.005) associated with the prevalence of MI in individuals with or without hypertension or diabetes mellitus: the C→T polymorphism (rs9925481) of the C-type lectin domain family 16, member A gene (CLEC16A; P = 0.0023; odds ratio, 0.61) in individuals without hypertension; the A→G polymorphism (rs12632110) of the sema domain, immuno-globulin domain, short basic domain, secreted, 3F gene (SEMA3F; P = 0.0028; odds ratio, 0.74) in individuals without diabetes mellitus; and the A→G polymorphism (rs7913948) of the arachidonate 5-lipoxygenase gene (ALOX5; P = 0.0008; odds ratio, 1.81) in individuals without hypertension or diabetes mellitus. No polymorphism was significantly associated with MI in individuals with hypertension, in those with diabetes mellitus, or in those with both conditions. In conclusion, genetic variants that confer susceptibility to MI differed among individuals with or without hypertension or diabetes mellitus. Stratification of subjects based on hypertension or diabetes mellitus may thus be important in order to achieve personalized prevention of MI with the use of genetic information.