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Although chronic kidney disease (CKD) is recognized as an important risk factor for myocardial infarction (MI), genetic factors underlying predisposition to MI in individuals with or without CKD remain largely unknown. The aim of the present study was to identify genetic variants that confer susceptibility to MI in individuals with or without CKD in order to allow prediction of genetic risk for such individuals separately. The study population comprised a total of 4344 individuals, including 1247 individuals with CKD (506 subjects with MI and 741 controls) and 3097 individuals without CKD (833 subjects with MI and 2264 controls). The 150 polymorphisms examined in this study were selected by genome-wide association studies of ischemic stroke and MI with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix) and determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. In individuals with CKD, no polymorphism was significantly related to MI. In individuals without CKD, an initial screen by the Chi-square test revealed that the Cyright curved arrow T polymorphism of CLEC16A (rs9925481) and the Aright curved arrow G polymorphism of LAMA3 (rs12373237) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the Cright curved arrow T polymorphism of CLEC16A (dominant model; P=0.0003; odds ratio, 0.66) and the Aright curved arrow G polymorphism of LAMA3 (recessive model; P=0.0087; odds ratio, 0.75) were significantly (P<0.05) associated with MI. A stepwise forward selection procedure also revealed that these polymorphisms were significant and independent determinants of MI. CLEC16A and LAMA3 may be susceptibility loci for MI in Japanese individuals without CKD. Determination of genotypes for CLEC16A and LAMA3 may prove informative for assessment of the genetic risk for MI in such individuals.

Although genetic epidemiological studies have implicated several genetic variants as risk factors for hemorrhagic stroke, the genetic determinants of this condition remain largely unknown. We examined an association of genetic variants with intracerebral or subarachnoid hemorrhage among Japanese individuals. The study population comprised 4,304 unrelated Japanese individuals, including 377 subjects with intracerebral hemorrhage, 205 subjects with subarachnoid hemorrhage, and 3,722 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the GeneChip Human Mapping 500K Array Set. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the C->T polymorphism (rs1324694) of ERLIN1, the C->T polymorphism (rs12679196) of TRAPPC9, and the G->T polymorphism (rs16936752) of WNK2 were significantly (P<0.05) associated with the prevalence of intracerebral hemorrhage, and that the A->G polymorphism (rs3111754) of ITM2C and the A->G polymorphism (rs10986769) of MAPKAP1 were significantly associated with the prevalence of subarachnoid hemorrhage. Genotypes for ERLIN1, TRAPPC9, and WNK2 may prove informative for assessment of the genetic risk for intracerebral hemorrhage, and those for ITM2C and MAPKAP1 may be beneficial in assessment of the genetic risk for subarachnoid hemorrhage in Japanese individuals.

Dyslipidemia is an important risk factor for myocardial infarction (MI). We previously showed that gene polymorphisms associated with MI differed among individuals with different lipid profiles. We further examined whether genetic variants that confer susceptibility to MI might differ among individuals with low or high serum concentrations of triglycerides, high density lipoprotein (HDL)-cholesterol, or low density lipoprotein (LDL)-cholesterol. The study population comprised 5270 Japanese individuals, including 1188 subjects with MI and 4082 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 the Affymetrix GeneChip Human Mapping 500K Array Set. The initial Chi-square test revealed that the A->G polymorphism (rs12632110) of SEMA3F was significantly (false discovery rate <0.05) associated with MI among individuals with high serum HDL-cholesterol or among those with low serum LDL-cholesterol. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that rs12632110 was significantly (P<0.01) associated with MI in individuals with high serum HDL-cholesterol or with low serum LDL-cholesterol. The genetic variants that confer susceptibility to MI differ among individuals with different lipid profiles, and the genetic component for the development of MI is more apparent in individuals at low-risk (high HDL- and low LDL-cholesterol levels) compared to those at high-risk. Stratification of subjects according to lipid profiles may thus be important for personalized prevention of MI based on genetic information.

Although metabolic syndrome has been recognized as a risk factor for ischemic stroke, genetic factors associated with ischemic stroke in individuals with metabolic syndrome remain unknown. We examined an association of genetic variants with ischemic stroke among individuals with or without metabolic syndrome. The study population comprised 4,387 unrelated Japanese individuals, including 1,884 individuals with metabolic syndrome (240 subjects with ischemic stroke and 1,644 controls) and 2,503 individuals without metabolic syndrome (280 subjects with ischemic stroke and 2,223 controls). The 150 polymorphisms examined in the present study were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). The initial chi-square test revealed that the Cright curved arrow T polymorphism (rs9925481) of CLEC16A and the Aright curved arrow G polymorphism (rs4923918) of SPTBN5 were significantly (P<0.005) associated with ischemic stroke among individuals with metabolic syndrome. No polymorphism was significantly associated with ischemic stroke among individuals without metabolic syndrome. Multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure revealed that the Aright curved arrow G polymorphism (rs4923918) of SPTBN5 was significantly (P<0.005), and the Cright curved arrow T polymorphism (rs9925481) of CLEC16A was almost significantly, associated with ischemic stroke in individuals with metabolic syndrome. Genetic variants that confer susceptibility to ischemic stroke may differ among individuals with or without metabolic syndrome. Stratification of subjects according to the presence or absence of metabolic syndrome may thus be important for personalized prevention of ischemic stroke based on genetic information.

Hypertension and diabetes mellitus are important risk factors for myocardial infarction (MI). The purpose of the present study was to identify genetic variants that confer susceptibility to MI in individuals with or without hypertension or diabetes mellitus, thereby contributing to the personalized prevention of MI in such individuals. The study population comprised 5,835 unrelated Japanese individuals, including 1,339 subjects with MI and 4,496 controls. The 150 polymorphisms were selected by genome-wide association studies of MI and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set. The genotypes for these polymorphisms were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. 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 of CLEC16A (rs9925481) in individuals without hypertension, the A --> G polymorphism of SEMA3F (rs12632110) in individuals without diabetes mellitus and the A --> G polymorphism of ALOX5 (rs7913948) 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. 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.

Chronic kidney disease (CKD) is recognized as a risk factor not only for end-stage renal disease but also for cardiovascular disease. Early detection and treatment of CKD is a likely key factor for prevention of its complications. Although genetic linkage analyses and association studies have implicated several loci and candidate genes in predisposition to CKD, the genes that underlie genetic susceptibility to this condition have remained largely unknown. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in Japanese individuals. The study population comprised 4,829 Japanese individuals (2,697 men, 2,132 women), including 757 subjects with CKD [464 men, 293 women; estimated glomerular filtration rate (eGFR) <50 ml min 1.73 m(-2)] and 4,072 controls (2,233 men, 1,839 women; eGFR >or=60 ml min 1.73 m(-2)). The genotypes for 40 polymorphisms of 39 candidate genes were determined. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that six polymorphisms of F10, PITRM1, PCSK2, JPH3, MYO7B, and AKAP12 were related (P<0.05) to the prevalence of CKD. Among these polymorphisms, the Cright curved arrow T polymorphism of F10 (rs5962) was most significantly associated with this condition. Determination of genotypes for the Cright curved arrow T polymorphism of F10 may prove informative for assessment of genetic risk for CKD in Japanese individuals.

The purpose of the present study was to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in individuals with low or high serum concentrations of triglycerides (TG), high-density lipoprotein (HDL)-cholesterol, or low-density lipoprotein (LDL)-cholesterol, thereby contributing to the personalized prevention of CKD in such individuals. The study population comprised 5944 Japanese individuals, including 1706 subjects with CKD [estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 4238 controls (eGFR>or=60 ml/min/1.73 m2). The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, and a stepwise forward selection procedure revealed that seven different polymorphisms were significantly (P<0.005) associated with the prevalence of CKD in individuals with low or high serum concentrations of TG or HDL- or LDL-cholesterol: the Aright curved arrow G (Glu23Lys) polymorphism of KCNJ11 and the 125592Cright curved arrow A (Thr431Asn) polymorphism of ROCK2 in individuals with low serum TG; the 734Cright curved arrow T (Thr254Ile) polymorphism of ACAT2 and the Cright curved arrow G (Gln27Glu) polymorphism of ADRB2 in individuals with high serum TG; the -1607/1Gright curved arrow 2G polymorphism of MMP1 in individuals with low serum HDL-cholesterol; the Gright curved arrow A (Val158Met) polymorphism of COMT in individuals with low serum LDL-cholesterol; the 584Gright curved arrow A (Gln192Arg) polymorphism of PON1 in individuals with high serum LDL-cholesterol. No polymorphism was associated with CKD in individuals with high serum HDL-cholesterol. These results suggest that polymorphisms associated with CKD may differ among individuals with different lipid profiles. Stratification of subjects according to lipid profiles may thus be important for personalized prevention of CKD based on genetic information.

The purpose of the present study was to identify genetic variants which confer susceptibility to chronic kidney disease (CKD) in high- or low-risk subjects defined by conventional risk factors separately. The study population comprised 2828 Japanese individuals, including 434 subjects with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and 2394 controls (eGFR > or =60 ml/min/ 1.73 m(2)). The 1012 high-risk subjects had both hypertension and diabetes mellitus, and the 1816 low-risk subjects had none of these conditions. The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that ten different polymorphisms were associated (P<0.05) with the prevalence of CKD in high- or low-risk subjects: the -519Aright curved arrow G polymorphism of MMP1, the 1061Aright curved arrow G (Ile405Val) polymorphism of CETP, the Aright curved arrow G (Lys45Glu) polymorphism of MMP3, the -219Gright curved arrow T polymorphism of APOE, the Aright curved arrow G (Ile1205Val) polymorphism of COL3A1, the -863Cright curved arrow A polymorphism of TNF, and the 1454Cright curved arrow G (Leu125Val) polymorphism of PECAM1 in high-risk subjects; and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2, the 2386Aright curved arrow G (Ile796Val) polymorphism of SCAP, and the TAAAright curved arrow del polymorphism of PDE4D in low-risk subjects. Among these polymorphisms, the -519Aright curved arrow G polymorphism of MMP1 and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2 were most significantly associated with CKD in high- or low-risk individuals, respectively. These results suggest that polymorphisms associated with CKD may differ among high- or low-risk subjects. Stratification of subjects according to conventional risk factors may thus be important for personalized prevention of CKD based on genetic information.

Although diabetes mellitus has been recognized as a risk factor for chronic kidney disease (CKD), genetic factors for predisposition to CKD in individuals with diabetes mellitus remain elucidated. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD among individuals with type 2 diabetes mellitus. The study population comprised 1742 Japanese individuals, including 636 subjects with CKD [estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 1106 controls (eGFR>or=60 ml/min/1.73 m2). The genotypes for 24 polymorphisms of 22 candidate genes were determined. An initial screen of allele frequencies by the Chi-square test revealed that four polymorphisms were significantly (false discovery rate<0.05) associated with the prevalence of CKD in individuals with type 2 diabetes mellitus. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the 8733T-->C polymorphism of ALOX5AP (rs3803278), the C-->T (Ser532Leu) polymorphism of IRAK1 (rs1059703), and the 2445G-->A (Ala54Thr) polymorphism of FABP2 (rs1799883) were significantly (P<0.05) associated with the prevalence of CKD. Our results suggest that ALOX5AP, IRAK1, and FABP2 are susceptibility loci for CKD among Japanese individuals with type 2 diabetes mellitus.

Metabolic syndrome is a risk factor for cardiovascular disease. The aim of the present study was to identify genetic variants that confer susceptibility to atherothrombotic cerebral infarction among individuals with metabolic syndrome in order to allow prediction of genetic risk for this condition. The study population comprised 1284 unrelated Japanese individuals with metabolic syndrome, including 313 subjects with atherothrombotic cerebral infarction and 971 controls. The genotypes for 296 polymorphisms of 202 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The Chi-square test, multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, hypercholesterolemia, and diabetes mellitus, as well as a stepwise forward selection procedure revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (rs529038) of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were associated (P<0.05) with the prevalence of atherothrombotic cerebral infarction. Among these polymorphisms, the 2445G-->A (Ala54Thr) polymorphism of FABP2 was most significantly associated with this condition. Our results suggest that FABP2, IPF1, FABP1, ROS1, ADIPOQ, ALOX5AP, NOS3, and LGALS2 are susceptibility loci for atherothrombotic cerebral infarction among Japanese individuals with metabolic syndrome. Genotypes for these polymorphisms, especially for the 2445G-->A (Ala54Thr) polymorphism of FABP2, may prove informative for the prediction of genetic risk for atherothrombotic cerebral infarction among such individuals.

Although various environmental factors, such as a high-salt diet, a smoking habit, excessive alcohol intake, and physical inactivity, influence the development of hypertension, genetic variation also contributes to an individual's susceptibility to this condition. The purpose of the present study was to identify gene polymorphisms that confer susceptibility or resistance to hypertension, and thereby contribute to the prediction of the genetic risk for this condition. The study population comprised 2752 unrelated Japanese individuals (1370 men, 1382 women), including 1276 subjects with hypertension (774 men, 502 women) and 1476 controls (596 men, 880 women). The genotypes for 50 polymorphisms of 35 candidate genes were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Evaluation of genotype distributions by the Chi-square test and subsequent multivariable logistic regression analysis with adjustment for age, sex, body mass index, smoking status, and the prevalence of diabetes mellitus and hypercholesterolemia revealed that the -14C-->T polymorphism of ABCA1, the C-->G (Ser2229Cys) polymorphism of ROS1, the C-->T (Asn591Asn) polymorphism of LDLR, the 13989A-->G (Ile118Val) polymorphism of CYP3A4, the C-->G and A-->C polymorphisms of ADIPOR1, and the -519A-->G polymorphism of MMP1 were significantly (P<0.05) associated with the prevalence of hypertension. Systolic and diastolic blood pressure differed significantly among genotypes for the -14C-->T polymorphism of ABCA1 and the C-->G (Ser2229Cys) polymorphism of ROS1, with the variant T and G alleles, respectively, being related to increased blood pressure. These results suggest that polymorphisms of ABCA1 and ROS1 are determinants of blood pressure and the development of hypertension in Japanese individuals. Determination of genotypes for ABCA1 and ROS1 may thus prove informative for the prediction of the genetic risk for hypertension.

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.

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 <0.05) associated with the prevalence of AF. The T allele of the MMP2 polymorphism and the C allele of the IL10 polymorphism were a risk factor for and protective factor against AF, respectively. Determination of the genotypes for these polymorphisms may thus prove informative for assessment of the genetic component of AF.

Type 2 diabetes mellitus is a complex metabolic disorder in which endogenous sex hormones may contribute to sex-dependent etiologies. We hypothesized that genetic variants related to type 2 diabetes mellitus might differ between men and women. We thus performed a large-scale association study to identify gene polymorphisms associated with type 2 diabetes mellitus in men and women separately. The study population comprised 4854 unrelated Japanese individuals (2688 men, 2166 women), including 1490 subjects with type 2 diabetes mellitus (969 men, 521 women). The genotypes for 16 gene polymorphisms were determined with 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, body mass index, and smoking status revealed that the T-->G (3' UTR) polymorphism of the thrombospondin 2 gene (THBS2), the -603A-->G polymorphism of the coagulation factor III gene (F3), and the G-->T (intron 2) polymorphism of the adipocyte, C1Q, and collagen domain containing (adiponectin) gene (ADIPOQ) were significantly associated with the prevalence of type 2 diabetes mellitus in men, and that the A-->G (Arg160Gly) polymorphism of the paraoxonase 1 gene (PON1) was significantly associated with this condition in women. A stepwise forward selection procedure demonstrated that genotypes of THBS2, F3, and ADIPOQ were significant determinants of type 2 diabetes mellitus in men, and that genotype of PON1 significantly affected this condition in women. Genotyping of these polymorphisms may prove informative for assessment of the genetic component of type 2 diabetes mellitus for men and women separately.

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: 1018Cright curved arrow T of GP1BA, -108/3Gright curved arrow 4G of IPF1, 677Cright curved arrow T of MTHFR, and Gright curved arrow A of UTS2 in hypertensive individuals; 2445Gright curved arrow A of FABP2, -108/3Gright curved arrow 4G of IPF1, 677Cright curved arrow T of MTHFR, -11,377Cright curved arrow G of ACDC, Aright curved arrow G of AKAP10, 11,496Gright curved arrow A of F7, and 46Cright curved arrow T of F12 in individuals without hypercholesterolemia; 2445Gright curved arrow A of FABP2 in diabetic individuals; and -108/3Gright curved arrow 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.

The aim of the present study was to assess the genetic risk for atherothrombotic cerebral infarction (ACI) in men and women separately as well as in individuals with or without conventional risk factors for atherosclerosis and thereby to contribute to the personalized prevention of ACI. The study population comprised 2705 unrelated Japanese individuals (1244 men, 1461 women), including 636 subjects (372 men, 264 women) with ACI. Subjects with ACI and controls either had or did not have conventional risk factors for atherosclerosis, including hypertension, hypercholesterolemia, and diabetes mellitus. The genotypes for 202 polymorphisms of 152 candidate genes were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis and a stepwise forward selection procedure revealed that 11 different polymorphisms were significantly (P < 0.005) associated with ACI in women or men or in individuals with or without hyper-tension, hypercholesterolemia, or diabetes mellitus: the 584C-->T polymorphism of LIPG, 5665G-->T of EDN1, and G-->A of CCL11 in women; 677C-->T of MTHFR, 1323C-->T of ITGB2, 3932T-->C of APOE, and -231A-->G of EDNRA in men; -572 G -->C of IL6 in hypertensive individuals; -403G-->A of CCL5 and G-->A of COMT in individuals with hypercholesterolemia; and 3932T--> C of APOE and A-->G of TNFSF4 in diabetic individuals. Polymorphisms associated with ACI may thus differ between women and men as well as among individuals with different risk factors. Stratification of subjects on the basis of sex or conventional risk factors for atherosclerosis may therefore be important in order to achieve the personalized prevention of ACI with the use of genetic information.

The purpose of the present study was to identify gene polymorphisms for the reliable assessment of genetic factors for obesity. The study population comprised 3906 unrelated Japanese individuals (2286 men, 1620 women), including 1196 subjects (677 men, 519 women) with obesity (body mass index of > or = 25 kg/m2) and 2710 controls (1609 men, 1101 women). The genotypes for 147 polymorphisms of 124 candidate genes were determined with 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, and the prevalence of smoking revealed that the -30Gright curved arrow A polymorphism of GCK, the -240Aright curved arrow T polymorphism of ACE, and the -482Cright curved arrow T polymorphism of APOC3 were significantly (P < 0.01) associated with the prevalence of obesity, and the -1989Tright curved arrow G polymorphism of ESR1 was almost significantly associated. A stepwise forward selection procedure demonstrated that ACE, GCK, and ESR1 genotypes significantly (P < 0.01) and independently affected the prevalence of obesity. Combined genotype analysis for these three polymorphisms yielded a lowest odds ratio of 0.45 for the combined genotypes of AT or TT for ACE, GG for GCK, and GG for ESR1 in comparison with the combined genotypes of AA for ACE, GG for GCK, and TT or TG for ESR1. Genotypes for ACE, GCK, and ESR1 may prove reliable for the assessment of genetic factors for obesity. Determination of the combined genotypes for these genes may contribute to the personalized prevention of this condition.

The purpose of the present study was to identify gene polymorphisms for reliable assessment of genetic factors for type 2 diabetes mellitus. The study population comprised 4853 unrelated Japanese individuals (2688 men, 2165 women), including 1489 subjects with type 2 diabetes mellitus (969 men, 520 women) and 3364 controls (1719 men, 1645 women). The genotypes for 148 polymorphisms of 124 candidate genes were determined with a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Sixteen polymorphisms were related (p<0.05) to the prevalence of type 2 diabetes mellitus as determined by the chi-square test. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of smoking revealed that, among these polymorphisms, the -603A --> G polymorphism of the gene for coagulation factor III (F3) was significantly (p<0.001) associated with the prevalence of type 2 diabetes mellitus, with the -603G allele representing a risk factor for this condition. A stepwise forward selection procedure demonstrated that F3 genotype (GG versus AA + AG) significantly (p<0.001) and independently affected the prevalence of type 2 diabetes mellitus. Genotype for F3 may prove reliable for assessment of genetic factors for type 2 diabetes mellitus. Determination of the genotype for this gene may contribute to personalized prevention of this condition.