Association of gene polymorphisms with myocardial infarction in individuals with or without conventional coronary risk factors

Abstract

The purpose of the present study was to assess the genetic risk for myocardial infarction (MI) in individuals with or without conventional coronary risk factors and thereby to contribute to the personalized prevention of MI in such individuals. The study population comprised 3483 unrelated Japanese individuals (1913 men, 1570 women). The 1192 subjects with MI (926 men, 266 women) and 2291 controls (987 men, 1304 women) either had or did not have conventional coronary risk factors, including hypertension, hypercholesterolemia, and diabetes mellitus. The genotypes for 164 polymorphisms of 137 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis and a stepwise forward selection procedure revealed that nine different polymorphisms were significantly (P<0.005) associated with MI among individuals with or without hypertension, hypercholesterolemia, or diabetes mellitus: 1018C→T of GP1BA, -108/3G→4G of IPF1, 677C→T of MTHFR, and G→A of UTS2 in hypertensive individuals; 2445G→A of FABP2, -108/3G→4G of IPF1, 677C→T of MTHFR, -11,377C→G of ACDC, A→G of AKAP10, 11,496G→A of F7, and 46C→T of F12 in individuals without hypercholesterolemia; 2445G→A of FABP2 in diabetic individuals; and -108/3G→4G of IPF1 in nondiabetic individuals. Polymorphisms associated with MI may thus differ among individuals with different conventional coronary risk factors. Stratification of subjects on the basis of such risk factors may thus be important in order to achieve personalized prevention of MI with the use of genetic information.