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Nagoya-shi, Japan

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. Source


Abe S.,Gifu Prefectural General Medical Center | Tokoro F.,Gifu Prefectural General Medical Center | Matsuoka R.,Gifu Prefectural General Medical Center | Arai M.,Gifu Prefectural General Medical Center | And 8 more authors.
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, hypo-high density lipoprotein (HDL)-cholesterolemia or hyper-low density lipoprotein (LDL)cholesterolemia in Japanese individuals with 29 polymorphisms observed to confer susceptibility for coronary heart disease. This was performed through meta-analyses of genome-wide association studies in Caucasian populations. The study population comprised 2,354 individuals with dyslipidemia (hypertriglyceridemia, hypo-HDL-cholesterolemia or hyper-LDL-cholesterolemia) 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=2.1x10-7), rs4845625 of interleukin 6 receptor (IL6R; FDR=0.032), rs46522 of ubiquitin-conjugating 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/serine-rich coiled-coil 1 (PSRC1; FDR=0.004) and rs2075650 of translocase of outer mitochondrial membrane 40 homolog (TOMM40; FDR=0.004) were significantly associated with hyper-LDL-cholesterolemia. Multivariate logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 of ZPR1 (P=5.1x10-7; 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 hyper-LDL-cholesterolemia. 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. Source


Yoshida T.,Inabe General Hospital | Kato K.,Meitoh Hospital | Kato K.,Mie University | Oguri M.,Red Cross | And 13 more authors.
International Journal of Molecular Medicine | Year: 2011

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=1.6×10-7; odds ratio, 2.32) hypertension; in individuals with (P=0.0002; odds ratio, 1.65) or without (P=8.1×10-7; odds ratio, 1.76) DM; and in individuals without CKD (P=6.0×10-11; 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) 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. Source


Yoshida T.,Inabe General Hospital | Kato K.,Meitoh Hospital | Kato K.,Mie University | Oguri M.,Red Cross | And 12 more authors.
Molecular Medicine Reports | Year: 2011

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 BTN2AI 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=3.1×10 -5; odds ratio, OR=1.66) or high (P=1.1×10 -6; OR=2.09) triglycerides; in individuals with low (P=0.0082; OR=1.75) or high (P=2.0x10 -9; OR=1.85) HDL cholesterol; and in individuals with low (P=3.2x10 -7; OR=1.75) or high (P=2.8×10 -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. Source


Yoshida T.,Inabe General Hospital | Kato K.,Meitoh Hospital | Kato K.,Mie University | Horibe H.,Gifu Prefectural Tajimi Hospital | And 7 more authors.
Nephrology | Year: 2011

Aim: Although recent genetic studies suggested that several genetic variants increase the risk for chronic kidney disease (CKD), the genes that underlie genetic susceptibility to this condition remain to be identified definitively. We showed that the C→T polymorphism (rs6929846) of BTN2A1 and A→G polymorphism (rs2569512) of ILF3 were significantly associated with myocardial infarction in Japanese individuals by a genome-wide association study. The purpose of the present study was to examine a possible association of these polymorphisms (rs6929846, rs2569512) with CKD in Japanese individuals. Methods: A total of 7542 Japanese individuals from two independent populations were examined: Subject panel A comprised 971 individuals with CKD (estimated glomerular filtration rate (eGFR) <60 mL/min 1.73 m -2)) and 2269 controls (eGFR ≥60 mL/min 1.73 m -2); and subject panel B comprised 1318 individuals with CKD and 2984 controls. Results: The ξ 2 test revealed that rs6929846 of BTN2A1, but not rs2569512 of ILF3, was significantly related to the prevalence of CKD both in subject panels A (P = 0.0383) and B (P = 0.0477). Multivariable logistic regression analysis with adjustment for covariates revealed that the C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with the prevalence of CKD in subject panels A (P = 0.0422; recessive model; odds ratio, 2.36) and B (P = 0.0386; dominant model; odds ratio, 1.21) with the T allele representing a risk for this condition. Conclusion: Our results suggest that BTN2A1 may be a susceptibility gene for CKD in Japanese individuals. Yoshida et al. found the polymorphism (rs6929846) of BTN2A1 was significantly associated with chronic kidney disease in a Japanese population, which validated their hypothesis based on their previous genome-wide association studies data. © 2011 Asian Pacific Society of Nephrology. Source

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