Association of gene polymorphisms with myocardial infarction in individuals with different lipid profiles.

ABSTRACT

Hyperlipidemia or dyslipidemia is one of the most important risk factors for coronary heart disease. The purpose of the present study was to identify gene polymorphisms for assessment of the genetic risk for myocardial infarction (MI) in individuals with low or high serum concentrations of high- density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, or triglyceride (TG), thereby contributing to the personalized prevention of MI in such individuals. The study population comprised 2682 unrelated Japanese individuals (1796 men, 886 women), including 1113 subjects (869 men, 244 women) with MI and 1569 controls (927 men, 642 women). 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 analyses and stepwise forward selection procedures revealed that seven different polymorphisms were significantly (P<0.005) associated with MI in individuals with low or high serum concentrations of HDL- or LDL-cholesterol or of TG the 190T --> C (Trp64Arg) polymorphism of ADRB3 in individuals with low HDL-cholesterol; the 1018C --> T (Thr145Met) polymorphism of GP1BA, the A --> G (Ile646Val) polymorphism of AKAP10, and the -55C --> T polymorphism of UCP3 in individuals with high HDL-cholesterol; the -603A --> G polymorphism of F3 and the -11377C --> G polymorphism of ADIPOQ in individuals with low LDL-cholesterol; the 1018C --> T polymorphism of GP1BA in individuals with low TG; and the 4G --> 5G polymorphism of PAI1 in individuals with high TG. No polymorphism was associated with MI in individuals with high LDL-cholesterol. These results suggest that polymorphisms associated with MI may differ among individuals with different lipid profiles. Stratification of subjects according to lipid profiles may thus be important for personalized prevention of MI based on genetic information.