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Yoshida T.,Inabe General Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 7 more authors.
International Journal of Molecular Medicine | Year: 2010

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. Source


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


Fujimaki T.,Gifu Prefectural Tajimi Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 9 more authors.
Atherosclerosis | Year: 2010

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. © 2009 Elsevier Ireland Ltd. Source


Nakano T.,Mie University | Okano H.,Suzuka General Hospital | Kobayashi M.,Yokkaichi Municipal Hospital | Ito K.,Mie Prefectural Shima Hospital | And 12 more authors.
Infection, Genetics and Evolution | Year: 2012

In Mie prefecture in Japan, 12 cases of sporadic hepatitis E occurred from 2004 to 2011. Mie prefecture is located in the central region of Japan, far from the most prevalent regions of hepatitis E virus (HEV) infection in Japan, the north and northeastern part. These 12 cases did not have any common risk factors of HEV infection. We analyzed the molecular epidemiology of the cases in Mie prefecture. We obtained the nucleotide sequences of the HEV strains and analyzed them with the sequences of other HEV strains by phylogenetic and coalescent analyses. Japan-indigenous genotype 3 HEV strains were divided into two major subtypes, namely, 3a and 3b; one minor subtype, 3e; and a few other unassigned lineages. The Japan-indigenous subtype 3e strains were closely related to European subtype 3e HEV strains and were comparatively rare in Japan; however, eight strains of the 12 cases we examined belonged to subtype 3e, indicating a close phylogenetic relationship, despite the lack of common risk factors. Coalescent analyses indicated that the Mie 3e strains seemed to have intruded into Mie prefecture about 10. years ago. Sporadic acute hepatitis E cases caused by the 3e strains occurred consistently from 2004 to 2011 in Mie prefecture. This is the first report of unexpected persistent occurrence of hepatitis by the European-type genotype 3 HEV, subtype 3e, in a country outside of Europe. Phylogenetic and coalescent analyses traced the history of the indigenization of the Mie 3e strains from Europe. Because hepatitis E cases caused by 3e strains are relatively rare in Japan, molecular evolutionary analyses of HEV infection in Mie prefecture is important for preventing a future hepatitis endemic or epidemic by 3e strains in Japan. © 2012 Elsevier B.V. Source


Oguri M.,Red Cross | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Yoshida T.,Inabe General Hospital | And 7 more authors.
American Journal of Hypertension | Year: 2010

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 χ2-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 djustment 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. © 2010 American Journal of Hypertension, Ltd. Source

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