A case of floating thrombus in the ascending aorta that caused recurrent peripheral arterial embolic events.

We report the case of a 62-year-old man with recurrent arterial embolisms to his arms caused by a thrombosis of the ascending aorta. He had developed a left brachial artery embolism 8 years previously, but presented with a right brachial artery embolus on this occasion. A clot-like mass was seen in the ascending aorta on computed tomography without significant atherosclerosis. Magnetic resonance imaging identified multiple asymptomatic cerebral infarctions. Therefore, we surgically removed the thrombus in the ascending aorta, which was an organized fibrin clot. Pathologically, atherosclerosis and plaque formation were evident at the intima where the clot attached. Clot formation was considered to be due to local arteriosclerosis. We report a case of thrombosis of the ascending aorta causing multiple and recurrent arterial embolisms. The patient had no evidence of coagulation disorders, and arteriosclerotic risk factors such as hypertension, diabetes mellitus, and dyslipidemia were absent. Thus, thrombosis may develop in patients without traditional risk factors. .

Impact of pitavastatin on high-sensitivity C-reactive protein and adiponectin in hypercholesterolemic patients with the metabolic syndrome: the PREMIUM Study.

BACKGROUND: Inflammatory reactions and oxidative stress, which are important in progression of atherosclerosis, are reported to be increased in individuals with metabolic syndrome (MetS). On the other hand, adiponectin levels are lowered. Since effects of pitavastatin on these parameters have not been reported in hypercholesterolemic patients with MetS, the present study was conducted. PURPOSE: To evaluate the effects of pitavastatin on inflammatory reaction, oxidative stress, and plasma adiponectin levels in hypercholesterolemic MetS patients in a multicenter trial. METHODS: This open-label, single group study was performed at 7 hospitals in Japan. Pitavastatin (2mg/day) was administered to 103 consecutive patients with hypercholesterolemia, subdivided into MetS and non-MetS for 12 weeks. Blood samples were collected after overnight fasting at the start of treatment (baseline) and after 12 weeks. RESULTS: In the patients with MetS (n=69), mean values of plasma high-sensitivity C-reactive protein (hs-CRP) were significantly higher and mean values of plasma high-molecular-weight (HMW)-adiponectin significantly lower than in their counterparts without MetS (n=34). The baseline HMW-adiponectin and high-density lipoprotein cholesterol (HDL-C) values significantly correlated only in the MetS patients (r=0.318; p=0.01). In an effectiveness analysis including 94 patients (62 with MetS, 32 without MetS), the level of hs-CRP was significantly decreased in patients with MetS during the drug treatment, whereas HMW-adiponectin did not change. When patients with MetS were divided into two subgroups according to the percent changes in HDL-C, significantly greater increase in HMW-adiponectin by pitavastatin treatment was observed in the HDL-C ≥10% increase subgroup than in the HDL-C <10% increase subgroup (p=0.009). CONCLUSION: Twelve weeks administration of pitavastatin, in addition to the antihyperlipidemic effects, may be beneficial as an anti-atherosclerotic therapy in hypercholesterolemic patients with MetS, taking changes in hs-CRP and HMW-adiponectin into consideration. ClinicalTrials.gov identifier: NCT00444717.

Association of a matrix metallopeptidase 1 gene polymorphism with long-term outcome of thoracic aortic aneurysm.

Although genetic variants are thought to contribute to the development of thoracic aortic aneurysm including dissection (TAA), it remains unclear whether gene polymorphisms are associated with the long-term outcome of TAA. The purpose of the present study was to identify genetic variants associated with the long-term outcome of medically treated patients with TAA. A total of 103 medically-treated patients with TAA (13 aneurysms and 90 dissections) were retrospectively studied for their outcomes (mean follow-up period, 24 months). The genotypes for 95 polymorphisms of 89 candidate genes were determined by 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 and subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the -340A→G polymorphism (rs514921) of the matrix metallopeptidase 1 gene (MMP1) was significantly (P=0.0288) associated with the outcome of TAA, with the minor G allele being related to a favorable outcome. The aneurysm diameter was significantly (P=0.0167) smaller in the combined group of the AG and GG genotypes for this polymorphism than in subjects with the AA genotype. Kaplan-Meier survival curves constructed according to MMP1 genotypes showed a more favorable outcome of TAA (log-rank P=0.0146) in subjects with the G allele of rs514921. Determination of genotype for this polymorphism may prove informative for assessment of the long-term outcome of TAA.

Association of a genetic variant of BTN2A1 with metabolic syndrome in East Asian populations.

BACKGROUND: The authors previously showed that the C→T polymorphism (rs6929846) of butyrophilin, subfamily 2, member A1 gene (BTN2A1) was significantly associated with myocardial infarction in Japanese individuals. Given that metabolic syndrome (MetS) is an important risk factor for myocardial infarction, the association of the rs6929846 of BTN2A1 with myocardial infarction might be attributable, at least in part, to its effect on susceptibility to MetS. AIM: The aim of the present study was to examine the relation of the rs6929846 of BTN2A1 to MetS in East Asian populations. METHODS: The study population comprised 5210 Japanese or Korean individuals (3982 individuals with MetS, 1228 controls) from three independent subject panels. Japanese subject panels A and B comprised 1322 individuals with MetS and 654 controls, and 1909 individuals with MetS and 170 controls, respectively, whereas the Korean population samples comprised 751 individuals with MetS and 404 controls. RESULTS: Comparison of genotype distributions using the χ(2) test revealed that the genotype distributions and allele frequencies of rs6929846 were significantly (p<0.05) associated with MetS in Japanese subject panels A (T allele frequency: MetS, 0.091; controls, 0.054; p=6.1×10(-5)) and B (T allele frequency: MetS, 0.091; controls, 0.039; p=0013) but not in the Korean population samples (T allele frequency: MetS, 0.102; controls, 0.125; p=0.0997). Multivariable logistic regression analysis with adjustment for covariates revealed that the rs6929846 of BTN2A1 was significantly (p<0.017) associated with MetS in Japanese subject panel A (p=0.0055, OR 1.97) and in all individuals (p=0.0038, OR 1.38), with the T allele representing a risk factor for this condition. CONCLUSION: BTN2A1 may be a susceptible gene for MetS in Japanese individuals.

Association of a polymorphism of BTN2A1 with hypertension in Japanese individuals.

BACKGROUND: We previously showed that the C→T polymorphism (rs6929846) in butyrophilin, subfamily 2, member A1 gene (BTN2A1) was associated with myocardial infarction in Japanese individuals. Given that hypertension is a major risk factor for myocardial infarction, the association of rs6929846 of BTN2A1 with myocardial infarction might be attributable, at least in part, to its effect on susceptibility to hypertension. We have thus examined the relation of rs6929846 of BTN2A1 to hypertension in Japanese individuals. METHODS: A total of 8,567 Japanese individuals from two independent subject panels were examined: Subject panels A and B comprised 2,317 hypertensive individuals and 1,933 controls, and 2,911 hypertensive individuals and 1,406 controls, respectively. The genotype of rs6929846 was determined by a method that combines the PCR and sequence-specific oligonucleotide probes with suspension array technology. RESULTS: Multivariable logistic regression analysis with adjustment for covariates revealed that rs6929846 of BTN2A1 was significantly associated with hypertension in subject panel A (P = 2.6 × 10(-6); odds ratio, 1.69) and in subject panel B (P = 0.0284; odds ratio, 1.24), with the T allele representing a risk factor for hypertension. The rs6929846 was associated with systolic blood pressure (BP) in subject panels A (P = 0.0063) and B (P = 0.0115) and with diastolic BP in subject panel B (P = 0.0323), with the T allele being related to high BP. CONCLUSIONS: BTN2A1 may be a susceptibility gene for hypertension in Japanese individuals. Determination of genotype for this polymorphism may prove informative for assessment of the genetic risk for hypertension.

Association of polymorphisms of BTN2A1 and ILF3 with myocardial infarction in Japanese individuals with different lipid profiles.

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 also showed that rs6929846 of BTN2A1 and rs2569512 of ILF3 were significantly associated with MI in Japanese individuals. In the present study, we examined the relationship between rs6929846 of BTN2A1 or rs2569512 of ILF3 and MI in individuals with low or high serum concentrations of triglycerides, high density lipoprotein (HDL) cholesterol, or low density lipoprotein (LDL) cholesterol, respectively. The study population comprised 5513 unrelated Japanese individuals, including 1537 subjects with MI and 3976 controls. Multivariable logistic regression analyses with adjustment for covariates revealed that rs6929846 of BTN2A1 was significantly associated with MI in individuals with low (P=3.1 x 10-5; odds ratio, OR=1.66) or high (P = 1.1 x 10⁻6; OR = 2.09) triglycerides; in individuals with low (P = 0.0082; OR = 1.75) or high (P = 2.0 x 10⁻9; OR = 1.85) HDL cholesterol; and in individuals with low (P = 3.2 x 10⁻7; OR = 1.75) or high (P = 2.8 x 10⁻5; OR =2.18) LDL cholesterol. Similar analyses revealed that rs2569512 of ILF3 was significantly associated with MI in individuals with low (P = 0.0066; OR = 1.47) or high (P = 0.0013; OR = 1.88) triglycerides; in individuals with low (P = 0.0059; OR = 1.96) or high (P = 0.0020; OR = 1.51) HDL cholesterol; and in individuals with low (P = 0.0004, OR = 1.62) LDL cholesterol, but not in those with high LDL cholesterol. The results suggest that the relationship between rs6929846 of BTN2A1 or rs2569512 of ILF3 and MI is influenced by the serum concentrations of HDL and LDL cholesterol, respectively. Stratification of subjects according to lipid profiles may thus be useful for the personalized prevention of MI based on genetic information.

Association of polymorphisms of BTN2A1 and ILF3 with myocardial infarction in Japanese individuals with or without hypertension, diabetes mellitus or chronic kidney disease.

Recent evidence suggests that genetic variants that confer susceptibility to myocardial infarction (MI) may differ between men and women or between individuals with or without conventional risk factors for MI. We previously showed that rs6929846 of BTN2A1 and rs2569512 of ILF3 were significantly associated with MI in Japanese individuals. In the present study, we examined the associations of rs6929846 of BTN2A1 or rs2569512 of ILF3 to MI among individuals stratified by the absence or presence of hypertension, diabetes mellitus (DM) and chronic kidney disease (CKD). The study population was comprised of 5689 unrelated Japanese individuals, including 1626 subjects with MI and 4063 controls with or without hypertension, DM or CKD. Multivariable logistic regression analyses with adjustment for covariates revealed that rs6929846 of BTN2A1 was significantly associated with MI in individuals with (P=0.0001; odds ratio, 1.49) or without (P=1.6x10-7; odds ratio, 2.32) hypertension; in individuals with (P=0.0002; odds ratio, 1.65) or without (P=8.1x10-7; odds ratio, 1.76) DM; and in individuals without CKD (P=6.0x10-11; odds ratio, 2.03), but not in those with CKD. Similar analyses revealed that rs2569512 of ILF3 was significantly associated with MI in individuals with (P=0.0041; odds ratio, 1.26) or without (P=0.0051; odds ratio, 1.78) hypertension; in individuals with (P=0.0200; odds ratio, 1.46) or without (P=0.0174; odds ratio, 1.43) DM; and in individuals with (P=0.0011, odds ratio, 1.47) or without (P=0.0237; odds ratio, 1.34) CKD. Results suggested that the association of rs6929846 in BTN2A1 with MI was more apparent in low-risk individuals than in high-risk individuals, whereas the association of rs2569512 in ILF3 with MI was not influenced by the absence or presence of hypertension, DM or CKD. Stratification of subjects based on hypertension, DM or CKD may thus be informative in order to achieve personalized prevention of MI with the use of genetic information.

Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.

OBJECTIVE: We have performed a genome-wide association study (GWAS) to identify genetic variants that confer susceptibility to myocardial infarction (MI) in Japanese and Korean populations. METHODS: A total of 17,447 Japanese or Korean individuals from four independent subject panels was examined. Japanese subject panels A, B, and C comprised 134 individuals with MI and 137 controls, 1431 individuals with MI and 3161 controls, and 643 individuals with MI and 1347 controls, respectively, whereas the Korean population comprised 1880 individuals with MI and 8714 controls. A GWAS for MI was performed in Japanese subject panel A with the use of the Affymetrix GeneChip Human Mapping 500K Array Set. RESULTS: Seventy single nucleotide polymorphisms (SNPs) significantly (P<1.0×10(-7)) associated with MI by the GWAS were examined further in Japanese subject panel B, revealing two SNPs (rs6929846 of BTN2A1, rs2569512 of ILF3) to be significantly (P<0.0007) associated with MI. The rs6929846 SNP of BTN2A1, but not rs2569512 of ILF3, was also significantly associated with MI in Japanese subject panel C. However, the association of neither rs6929846 nor rs2569512 with MI was replicated in the Korean population. CONCLUSION: BTN2A1 may be a susceptibility gene for MI in Japanese individuals.

Association of a polymorphism of BTN2A1 with chronic kidney disease in individuals with or without hypertension or diabetes mellitus.

Hypertension and diabetes mellitus are important risk factors for chronic kidney disease (CKD). We previously showed that the C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with myocardial infarction. The purpose of the present study was to examine an association of rs6929846 of BTN2A1 with CKD in individuals with or without hypertension or diabetes mellitus, thereby contributing to the personalized prevention of CKD in such individuals separately. The study population comprised 7,542 unrelated individuals, including 2,289 subjects with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and 5,253 controls (eGFR ≥60 ml/min/1.73 m(2)) with or without hypertension or diabetes mellitus. The Chi-square test, a multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with CKD in normotensive individuals, in diabetic individuals and in individuals with hypertension and diabetes mellitus, or without either condition, with the T allele representing a risk factor for CKD. Stratification of subjects based on hypertension or diabetes mellitus may thus be important in order to achieve personalized prevention of CKD with the use of genetic information.

Association of a polymorphism of BTN2A1 with dyslipidemia in East Asian populations.

We previously identified rs6929846 of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) as a susceptibility locus for myocardial infarction in Japanese individuals by a genome-wide association study. The aim of the present study was to examine the relation of the rs6929846 polymorphism of BTN2A1 to dyslipidemia in Japanese and Korean populations, given that dyslipidemia is an important risk factor for myocardial infarction. A total of 10,953 individuals from three independent subject panels were examined. The relations of the rs6929846 polymorphism of BTN2A1 to serum concentrations of triglycerides, high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol were examined in each subject panel. The C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with serum concentrations of triglycerides in Japanese subject panels A (P=0.0004) and B (P=0.0010), and in the Korean population (P=0.0095), with the minor T allele being related to an increased serum concentration of triglycerides. The rs6929846 was associated with serum concentrations of HDL-cholesterol in Japanese subject panels A (P=0.0047) and B (P=0.0015), with the T allele being related to a decreased serum concentration of HDL-cholesterol, but not in the Korean population. This polymorphism was associated with the serum concentration of LDL-cholesterol only in Japanese subject panel B (P=0.0059), with the T allele being related to an increased serum concentration of LDL-cholesterol. The results suggest that BTN2A1 may be a susceptibility gene for hypertriglyceridemia in East Asian populations and for low serum HDL-cholesterol in the Japanese population.

Genetic risk for myocardial infarction in Japanese individuals with or without chronic kidney disease.

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.

Association of genetic variants with myocardial infarction in Japanese individuals with different lipid profiles.

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.

Association of genetic variants with hemorrhagic stroke in Japanese 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.

Association of genetic variants with ischemic stroke in Japanese individuals with or without metabolic syndrome.

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.

Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals.

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease. Although genetic studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. The purpose of the present study was to identify genetic variants that confer susceptibility to hypertension in Japanese individuals. METHODS: A total of 5,734 Japanese individuals from two independent populations were examined: subject panel A comprised 2,066 hypertensive individuals and 824 controls; and subject panel B comprised 834 hypertensive individuals and 2,010 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of myocardial infarction and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). RESULTS: The chi(2)-test revealed that 10 polymorphisms were significantly (P < 0.05) related to the prevalence of hypertension in subject panel A. To validate the relations, these polymorphisms were examined in subject panel B. The A-->G polymorphism (rs645106) of SDK1 and the C-->G polymorphism (rs12078839) of RABGAP1L were significantly associated with hypertension in subject panel B. Multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the A-->G polymorphism of SDK1 was significantly associated with hypertension in both subject panels A and B, with the G allele protecting against this condition. CONCLUSIONS: SDK1 may be a susceptibility gene for hypertension in Japanese individuals, although the functional relevance of the identified polymorphism was not determined.

Association of genetic variants with chronic kidney disease in Japanese individuals with or without hypertension or diabetes mellitus.

Hypertension and diabetes mellitus are important risk factors for chronic kidney disease (CKD). The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in individuals with or without hypertension or diabetes mellitus, thereby contributing to the personalized prevention of CKD in such individuals separately. The study population comprised 5835 unrelated Japanese individuals, including 1763 subjects with CKD and 4072 controls. The 150 polymorphisms 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 genotypes for these polymorphisms were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The χ(2) test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that two different polymorphisms were significantly (P<0.005) associated with the prevalence of CKD in individuals with or without hypertension or diabetes mellitus: the A→G (Lys625Arg) polymorphism of CDH4 (rs6142884) in individuals without diabetes mellitus, and the C→T polymorphism of PTPRN2 (rs1638021) in individuals with hypertension and diabetes mellitus. No polymorphism was significantly associated with CKD in individuals with or without hypertension, in those with diabetes mellitus, or in those without hypertension or diabetes mellitus. Stratification of subjects based on hypertension or diabetes mellitus may thus be fundamental to achieving the personalized prevention of CKD with the use of genetic information.

Association of genetic variants with myocardial infarction in Japanese individuals with or without metabolic syndrome.

The etiology of metabolic syndrome (MetS) is highly complex, with both genetic and environmental factors being thought to play an important role. Although MetS has been recognized as a risk factor for myocardial infarction (MI), the genetic risk for MI in individuals with or without MetS has remained uncharacterized. We examined a possible association of genetic variants with MI in individuals with or without MetS separately. The study population comprised 4,424 individuals, including 1,918 individuals with MetS (903 subjects with MI and 1,015 controls) and 2,506 individuals without MetS (499 subjects with MI and 2,007 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 Affymetrix GeneChip Human Mapping 500K Array Set. Initial screening by the Chi-square test revealed that the C→T polymorphism (rs1794429) of LRPAP1, the A→G polymorphism (rs12373237) of LAMA3 and the A→G polymorphism (rs3782257) of NCOR2 were significantly (false discovery rate of <0.05) associated with MI for individuals with MetS, and that the C→G polymorphism (rs13051704) of TFF1 was significantly related to MI for individuals without MetS. Subsequent multivariable logistic analysis with adjustment for covariates revealed that rs1794429 of LRPAP1 (recessive model; P=0.0218; odds ratio=0.71) and rs3782257 of NCOR2 (dominant model; P=0.0057; odds ratio=1.94) were significantly associated with MI among individuals with MetS, and that rs13051704 of TFF1 (additive model; P=0.0100; odds ratio=0.55) was significantly associated with MI among individuals without MetS. The genetic variants that confer susceptibility to MI differ between individuals with or without MetS. Stratification of subjects according to the presence or absence of MetS may thus be important for personalized prevention of MI based on genetic information.

Association of genetic variants in SEMA3F, CLEC16A, LAMA3, and PCSK2 with myocardial infarction in Japanese individuals.

OBJECTIVE: The purpose of the present study was to identify genetic variants that confer susceptibility to myocardial infarction (MI) in Japanese individuals. METHODS: The study population comprised 5014 Japanese individuals, including 1444 subjects with MI and 3570 controls. The 150 polymorphisms examined in the present study were selected by a genome-wide association study for ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix), and were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. RESULTS: An initial screen by the chi-square test revealed that the A-->G polymorphism of SEMA3F (rs12632110), the C-->T polymorphism of CLEC16A (rs9925481), the A-->G polymorphism of LAMA3 (rs12373237), and the C-->G polymorphism of PCSK2 (rs6080699) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure revealed that the A-->G polymorphism of SEMA3F (dominant model; P=0.0014; odds ratio, 0.76), the C-->T polymorphism of CLEC16A (dominant model; P=0.0009; odds ratio, 0.75), the A-->G polymorphism of LAMA3 (recessive model; P=0.0099; odds ratio, 0.80), and the C-->G polymorphism of PCSK2 (recessive model; P=0.0155; odds ratio, 1.19) were significantly (P<0.05) associated with the prevalence of MI. CONCLUSION: Determination of these genotypes may prove informative for assessment of the genetic risk for MI in Japanese individuals.

Association of genetic variants with myocardial infarction in individuals with or without hypertension or diabetes mellitus.

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.