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Although several environmental factors, including a high-calorie diet and physical inactivity, influence the development of type 2 diabetes mellitus, genetic factors have been shown to contribute to individual susceptibility to this condition. The purpose of the present study was to identify gene polymorphisms that confer susceptibility or resistance to type 2 diabetes mellitus, and thereby to contribute to assessment of the genetic risk for this condition. The study population comprised 5259 unrelated Japanese individuals (2980 men, 2279 women), including 1640 subjects with type 2 diabetes mellitus (1071 men, 569 women) and 3619 controls (1909 men, 1710 women). The genotypes for 94 polymorphisms of 67 genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Evaluation of genotype distributions by the chi-square test revealed that the 13989-->G (Ile118Val) polymorphism of the cytochrome P450, subfamily IIIA, polypeptide 4 gene (CYP3A4) was significantly (false discovery rate, 0.000009) associated with the prevalence of type 2 diabetes mellitus. Multivariable logistic regression analysis with adjustment for age and sex also revealed that the 13989-->G (Ile118Val) polymorphism of CYP3A4 was significantly (P=0.00002) associated with the prevalence of type 2 diabetes mellitus, with the AG genotype being protective against this condition. Genotyping for CYP3A4 may thus prove informative for assessment of the genetic risk for type 2 diabetes mellitus.

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 (P0.005) 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.

Atrial fibrillation (AF) may result from an electric conduction disturbance, increased hemodynamic stress, ischemia, inflammation, or remodeling in atria. Although genetic epidemiological studies have identified several genetic variants as risk factors for AF, the genetic determinants of this condition remain largely unknown. The purpose of the present study was to identify gene polymorphisms that confer susceptibility to lone AF. The study population comprised 1069 unrelated Japanese individuals, including 196 subjects with chronic lone AF and 873 controls. The genotypes for 40 polymorphisms of 32 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 with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hyperchole-sterolemia as well as a stepwise forward selection procedure revealed that the -1306C-->T polymorphism of the matrix metalloproteinase 2 gene (MMP2) and the -592A-->C polymorphism of the interleukin 10 gene (IL10) were significantly (false discovery rate of

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