Meitoh Hospital

Nagoya-shi, Japan

Meitoh Hospital

Nagoya-shi, Japan
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Kato K.,Meitoh Hospital | Kato K.,Mie University | Tokuda Y.,Chubu Rosai Hospital | Inagaki N.,Gifu Prefectural Tajimi Hospital | And 7 more authors.
International Journal of Molecular Medicine | Year: 2012

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.


Hiramatsu M.,Nagoya Central Hospital | Oguri M.,Red Cross | Kato K.,Meitoh Hospital | Kato K.,Mie University | And 10 more authors.
International Journal of Molecular Medicine | Year: 2012

We previously showed that the -1131T→C polymorphism (rs662799) of the apolipoprotein A-V gene (APOA5) and the C.T polymorphism (rs6929846) of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) were significantly associated with an increased serum concentration of triglycerides, a decreased serum concentration of high density lipoprotein (HDL)-cholesterol, and the prevalence of metabolic syndrome (MetS) in Japanese individuals. The purpose of the present study was to examine whether these polymorphisms synergistically affect the prevalence of dyslipidemia and MetS in East Asian populations. The study populations comprised 7471 Japanese and 3529 Korean individuals in the dyslipidemia study, and 3474 Japanese and 1671 Korean individuals in the MetS study. Multivariable logistic regression analysis of combined genotypes with adjustment for age, gender and diabetes mellitus revealed that rs662799 and rs6929846 significantly and synergistically affected dyslipidemia. Japanese or Korean individuals with the C allele of APOA5 and the T allele of BTN2A1 had a 2.05- or 1.92-fold increased risk for hypertriglyceridemia and a 1.82- or 1.56-fold increased risk for hypo-HDL-cholesterolemia, respectively, compared to those with the TT genotype of APOA5 and the CC genotype of BTN2A1. Similar analysis with adjustment for age and gender revealed that Japanese individuals, but not Korean individuals, with the C allele of APOA5 and the T allele of BTN2A1 had a 2.87-fold increased risk for MetS compared to those with the TT genotype of APOA5 and the CC genotype of BTN2A1. Genetic variants of APOA5 and BTN2A1 may synergistically affect the prevalence of dyslipidemia in East Asian populations and of MetS in Japanese individuals.


Horibe H.,Gifu Prefectural Tajimi Hospital | Ueyama C.,Gifu Prefectural Tajimi Hospital | Fujimaki T.,Inabe General Hospital | Oguri M.,Red Cross | And 4 more authors.
Molecular Medicine Reports | Year: 2014

We have previously shown that the C→T polymorphism (rs6929846) of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) was significantly associated with myocardial infarction. Considering that dyslipidemia is a significant risk factor for coronary heart disease, it was hypothesized that the association between rs6929846 of BTN2A1 and myocardial infarction may be attributable, at least in part, to its effect on the susceptibility to dyslipidemia. The purpose of the present study was to examine a possible association of rs6929846 of BTN2A1 with dyslipidemia in community-dwelling individuals. The study subjects were comprised of 5,958 community-dwelling individuals (2,909 subjects with dyslipidemia and 3,049 controls) who were recruited into a population-based cohort study in Inabe, Japan. Dyslipidemia was defined by a serum concentration of triglycerides of ≥1.65 mmol/l, a serum high-density lipoprotein- cholesterol concentration of <1.04 mmol/l or a serum low-density lipoprotein (LDL)-cholesterol concentration of ≥3.64 mmol/l. A comparison of the allele frequencies or genotype distributions by the χ2 test revealed that rs6929846 of BTN2A1 was significantly associated with dyslipidemia (P<0.05). A multivariable logistic regression analysis adjusted for age, gender, body mass index, smoking status and the prevalence of diabetes mellitus revealed that rs6929846 of BTN2A1 was significantly (dominant model; P=2.4x10-4; odds ratio, 1.29) associated with dyslipidemia, with the minor T allele representing a risk for this condition. Among all the individuals, the serum concentrations of total cholesterol, triglycerides and LDL-cholesterol were significantly greater for individuals in the combined CT and TT genotype groups than for those with the CC genotype. BTN2A1 may thus be a susceptibility gene for dyslipidemia in community-dwelling individuals.


Matsuoka R.,Gifu Prefectural General Medical Center | Abe S.,Gifu Prefectural General Medical Center | Tokoro F.,Gifu Prefectural General Medical Center | Arai M.,Gifu Prefectural General Medical Center | And 8 more authors.
International Journal of Molecular Medicine | Year: 2015

Although various genes that confer susceptibility to myocardial infarction (MI) have been identified for Caucasian populations in genome-wide association studies (GWAS), genetic variants related to this condition in Japanese individuals have not been identife d definit ively. The a im of the present st udy was to examine an association of MI in Japanese individuals with 29 polymorphisms identified as susceptibility loci for MI or coronary artery disease in Caucasian populations by metaanalyses of GWAS. The study subjects comprised 1,824 subjects with MI and 2,329 controls. Genotypes of the polymorphisms were determined by Luminex bead-based multiplex assay. To compensate for multiple comparisons, we adopted the criterion of a false discovery rate (FDR) of <0.05 for statistical signifcance for association. Comparisons of allele frequencies by the?2 test revealed that rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1, FDR=0.0007), rs4977574 of the CDKN2B antisense RNA 1 gene (CDKN2B-AS1, F DR= 0. 0038), rs264 of the lipoprotein lipase gene (LPL, FDR=0.0061), rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1, FDR=0.0118), rs9319428 of the fms-related tyrosine kinase 1 gene (FLT1, FDR=0.0118) and rs12413409 of the cyclin and CBS domain divalent metal cation transport mediator 2 gene (CNNM2, FDR=0.0300) were significantly associated with MI. Multivariate logistic regression analysis with adjustment for covariates revealed that rs9369640 (P=0.0005; odds ratio, 0.89), rs4977574 (P=0.0001; odds ratio, 1.50), rs264 (P=0.0405; odds ratio, 0.85), rs599839 (P=0.0003; odds ratio, 0.68), rs9319428 (P=0.0155; odds ratio, 1.20) and rs12413409 (P=0.0076; odds ratio, 0.66) were significantly (P<0.05) associated with MI. PHACTR1, CDKN2B-AS1, LPL, PSRC1, FLT1 and CNNM2 may thus be susceptibility loci for MI in Japanese individuals.


Horibe H.,Gifu Prefectural Tajimi Hospital | Fujimaki T.,Inabe General Hospital | Oguri M.,Red Cross | Kato K.,Meitoh Hospital | And 8 more authors.
Nephrology | Year: 2015

Aim Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified in Caucasian populations by genome-wide association studies (GWASs). The aim of the present study was to examine a possible association of chronic kidney disease (CKD) with 29 polymorphisms previously identified as susceptibility loci for CAD by meta-analyses of GWASs. Methods The study population comprised 2247 Japanese individuals, including 1588 subjects with CKD [estimated glomerular filtration rate (eGFR) of <60mLmin-1 1.73m-2] and 659 controls (eGFR of ≥90mLmin-1 1.73m-2). The genotypes for 29 polymorphisms of 28 candidate genes were determined. Results The χ2 test revealed that rs4845625 (T→C) of IL6R, rs4773144 (A→G) of COL4A1, rs9319428 (G→A) of FLT1, and rs46522 (T→C) of UBE2Z were significantly (P<0.05) related to CKD. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidaemia revealed that rs4845625 of IL6R (P=0.0008; dominant model; odds ratio, 1.49), rs4773144 of COL4A1 (P=0.0252; dominant model; odds ratio, 1.28), and rs9319428 of FLT1 (P=0.0260: additive model; odds ratio, 0.77) were significantly associated with CKD. The serum concentration of creatinine was significantly (P=0.0065) greater and eGFR was significantly (P=0.0009) lower in individuals with the TC or CC genotype of IL6R than in those with the TT genotype. Conclusion The rs4845625 of IL6R may be a susceptibility locus for CKD in Japanese individuals. Summary at a Glance The authors detected a novel SNP in the IL6R gene that correlates with CKD in a reasonably large Japanese cohort. © 2014 Asian Pacific Society of Nephrology.


PubMed | Red Cross, Gifu University, Meitoh Hospital, Gifu Prefectural Tajimi Hospital and 3 more.
Type: Journal Article | Journal: Molecular medicine reports | Year: 2015

Although genetic variants, which regulate lipid metabolism, have been extensively investigated in Caucasian populations, the genes, which confer susceptibility to dyslipidemia in Japanese individuals, remain to be elucidated. The aim of the present study was to examine a possible association among hypertriglyceridemia, hypohigh density lipoprotein (HDL)cholesterolemia or hyperlow density lipoprotein (LDL)cholesterolemia in Japanese individuals with 29 polymorphisms observed to confer susceptibility for coronary heart disease. This was performed through metaanalyses of genomewide association studies in Caucasian populations. The study population comprised 2,354 individuals with dyslipidemia (hypertriglyceridemia, hypoHDLcholesterolemia or hyperLDLcholesterolemia) and 3,106 control individuals. To compensate for multiple comparisons of genotypes, a false discovery rate (FDR) of <0.05 was adopted to determine the statistical significance of the associations. Comparisons of allele frequencies using the 2 test revealed that rs964184 of zinc finger gene (ZPR1; FDR=2.1x107), rs4845625 of interleukin 6 receptor (IL6R; FDR=0.032), rs46522 of ubiquitinconjugating enzyme E2Z gene (UBE2Z; FDR=0.032) and rs17514846 of furin (FDR=0.041) were significantly associated with hypertriglyceridemia. The 2 test revealed that rs599839 of proline/serinerich coiledcoil 1 (PSRC1; FDR=0.004) and rs2075650 of translocase of outer mitochondrial membrane 40 homolog (TOMM40; FDR=0.004) were significantly associated with hyperLDLcholesterolemia. Multivariate logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 of ZPR1 (P=5.1x107; odds ratio, 1.37; dominant model), rs4845625 of IL6R (P=0.0019, odds ratio, 1.25; dominant model) and rs46522 of UBE2Z (P=0.0039, odds ratio, 1.19; dominant model) were significantly associated with hypertriglyceridemia, and that rs599839 of PSRC1 (P=0.0004, odds ratio, 0.70; dominant model) and rs2075650 of TOMM40 (P=0.0004, odds ratio, 1.43; dominant model) were significantly associated with hyperLDLcholesterolemia. Therefore, ZPR1, IL6R, and UBE2Z may be susceptibility loci for hypertriglyceridemia, whereas PSRC1 and TOMM40 may be such loci for hyper-LDL-cholesterolemia in Japanese individuals.


PubMed | Red Cross, Gifu University, Meitoh Hospital, Gifu Prefectural Tajimi Hospital and 3 more.
Type: Journal Article | Journal: International journal of molecular medicine | Year: 2015

Although various genes that confer susceptibility to myocardial infarction (MI) have been identified for Caucasian populations in genome-wide association studies (GWAS), genetic variants related to this condition in Japanese individuals have not been identified definitively. The aim of the present study was to examine an association of MI in Japanese individuals with 29 polymorphisms identified as susceptibility loci for MI or coronary artery disease in Caucasian populations by meta-analyses of GWAS. The study subjects comprised 1,824 subjects with MI and 2,329 controls. Genotypes of the polymorphisms were determined by Luminex bead-based multiplex assay. To compensate for multiple comparisons, we adopted the criterion of a false discovery rate (FDR) of <0.05 for statistical significance for association. Comparisons of allele frequencies by the (2) test revealed that rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1, FDR=0.0007), rs4977574 of the CDKN2B antisense RNA 1 gene (CDKN2B-AS1, FDR=0.0038), rs264 of the lipoprotein lipase gene (LPL, FDR=0.0061), rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1, FDR=0.0118), rs9319428 of the fms-related tyrosine kinase 1 gene (FLT1, FDR=0.0118) and rs12413409 of the cyclin and CBS domain divalent metal cation transport mediator 2 gene (CNNM2, FDR=0.0300) were significantly associated with MI. Multivariate logistic regression analysis with adjustment for covariates revealed that rs9369640 (P=0.0005; odds ratio, 0.89), rs4977574 (P=0.0001; odds ratio, 1.50), rs264 (P=0.0405; odds ratio, 0.85), rs599839 (P=0.0003; odds ratio, 0.68), rs9319428 (P=0.0155; odds ratio, 1.20) and rs12413409 (P=0.0076; odds ratio, 0.66) were significantly (P<0.05) associated with MI. PHACTR1, CDKN2B-AS1, LPL, PSRC1, FLT1 and CNNM2 may thus be susceptibility loci for MI in Japanese individuals.


PubMed | Kasugai Municipal Hospital, Meitoh Hospital, Gifu Prefectural Tajimi Hospital, Inabe General Hospital and 3 more.
Type: Journal Article | Journal: Biomedical reports | Year: 2016

Recent genome-wide association studies (GWASs) identified various genes and loci that confer susceptibility to coronary artery disease or myocardial infarction among Caucasian populations. As myocardial ischemia is an important risk factor for atrial fibrillation, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to atrial fibrillation through affecting the susceptibility to coronary artery disease. The aim of the present study was to examine the possible association of atrial fibrillation in Japanese individuals with 29 polymorphisms identified as susceptibility loci for coronary artery disease or myocardial infarction in the meta-analyses of GWASs in Caucasian populations. The study subjects comprised 5,470 Japanese individuals (305 subjects with atrial fibrillation and 5,165 controls). Genotypes for 29 polymorphisms were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the


PubMed | Red Cross, Meitoh Hospital, Gifu Prefectural Tajimi Hospital, Inabe General Hospital and 3 more.
Type: Journal Article | Journal: Biomedical reports | Year: 2015

Although genome-wide association studies (GWASs) have identified various genes and loci in predisposition to metabolic syndrome (MetS) or each component of this condition, the genetic basis of MetS in individuals remains to be identified definitively. The aim of the present study was to examine the possible association of MetS in individuals with 29 polymorphisms that were previously identified as susceptibility loci for coronary artery disease or myocardial infarction by meta-analyses of GWASs. The study population comprised 1,822 subjects with MetS and 1,096 controls. Subjects with MetS had 3 of the 5 components of the diagnostic criteria for MetS, whereas control individuals had 0-1 of the 5 components. The genotypes for the 29 polymorphisms were determined by the multiplex bead-based Luminex assay. Comparisons of allele frequencies by the


Yamada Y.,Mie University | Nishida T.,Mie University | Horibe H.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 3 more authors.
International Journal of Molecular Medicine | Year: 2014

Epigenetic modification, particularly changes in DNA methylation at gene promoters, is implicated in the pathogenesis of atherosclerosis. However, the analysis of DNA methylation in atherosclerosis has been limited to a few selected candidate genes. In this study, we therefore performed a genome-wide analysis of DNA methylation in the atherosclerotic human aorta. A total of 48 post-mortem human aortic intima specimens were examined. To avoid the effects of interindividual variation, we performed intraindividual paired comparisons between atheromatous plaque lesions and corresponding plaque-free tissue for 24 subjects. Bisulfite-modified genomic DNA was analyzed for DNA methylation with a specific microarray (Illumina HumanMethylation450 BeadChip). We compensated for multiple comparisons by applying Bonferroni's correction for statistical significance of association. DNA methylation was significantly (P<1.03×10-7) reduced at 15 CpG sites in 14 genes and increased at 30 CpG sites in 22 genes in atheromatous plaque compared with plaque-free intima. Three of the hypomethylated genes [Drosophila headcase (HECA), early B-cell factor 1 (EBF1) and nucleotide-binding oligomerization domain containing 2 (NOD2)] and three of the hypermethylated genes [human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), zinc finger E-box binding homeobox 1 (ZEB1) and FYN] were previously been implicated in atherosclerosis. The overexpression of HECA, EBF1 or NOD2 or the suppression of MAP4K4, ZEB1 or FYN expression in cultured HEK293 cells resulted in significant (P<4.80×10-7) changes in the expression of atherosclerosis-related genes, as determined with an expression microarray (Illumina HumanHT-12 v4 Expression BeadChip). Our findings suggested that HECA, EBF1 and NOD2 were significantly hypomethylated, whereas MAP4K4, ZEB1 and FYN were hypermethylated, in atheromatous plaque lesions compared with plaque-free intima. Epigenetic mechanisms may thus contribute to the pathogenesis of atherosclerosis.

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