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Identification of genes associated with bronchial asthtima, atopy, schizophrenia, and abnormal serum lipid profile

Research Project

Project/Area Number 12204001
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionUniversity of Tsukuba

Principal Investigator

ARINAMI Tadao  University of Tsukuba, Basic Medical Scienoes, Professor, 基礎医学系, 教授 (10212648)

Co-Investigator(Kenkyū-buntansha) NOGUCHI Emiko  University of Tsukuba, Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (40344882)
SHIMOKAWA Hiroaki  Kyushu Unviersity, faculty of Medical Sciences, Associate Professor, 大学院医学研究院, 助教授 (00235681)
柴崎 正直 (柴崎 正修)  筑波技術短期大学, 教授 (30049233)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥107,800,000 (Direct Cost: ¥107,800,000)
Fiscal Year 2004: ¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 2003: ¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 2002: ¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 2001: ¥30,000,000 (Direct Cost: ¥30,000,000)
Keywordsbronchial asthma / seasonal rhinitis / atopy / schizophrenia / genome / genetic polymorphism / genetic linkage / genetic association / 血清脂質 / 総合失調症 / 血清脂質異常 / 心筋梗塞 / 関連遺伝子 / 精神分裂病 / かもがや花粉症 / 罹患同胞対法 / 連鎖解析
Research Abstract

The purpose of this project is to identify genes associated with bronchial asthma, atopic dermatitis, seasonal rhinitis, schizophrenia, abnormal serum lipid profiles, and myocardial infarction. The screening methods we used were linkage analyses of families with multiple affected members and linkage disequilibrium mapping by transmission disequilibrium tests (TDT) to pinpoint associated genes.
We found strong evidence for linkage between mite-sensitive asthma and markers on chromosome 5q33 in our Japanese families. We performed mutation screening and association analyses of genes in the 9.4-Mb human linkage region and found that the CYFIP2 gene were associated significantly with asthma. Subjects homozygous for the haplotype overtransmitted to asthma-affected offspring showed significantly increased level of CYFIP2 gene expression in lymphocytes compared with ones heterozygous for the haplotype. TNF, LTA, and LTB is located consecutively on human chromosome 6p21 region, which has been li … More nked to asthma by several genome-wide screens including us. We screened for mutations in the coding and promoter regions of genes in the TNF-LTA region and conducted a TDT. Haplotypes of the LTA/TNF linkage disequilibrium block, which were associated with transcription ability changes, were associated significantly with asthma. Our results suggest that LTA is one of the genes contributing to susceptibility to atopic asthma. We identified linkage regions of chromosomes 1p, 4q, and 9q to seasonal allergic rhinitis (SAR) against orchard grass pollens. We screened for associations and found that that SNPs in SDAD1, CXCL9; CXCL10; and CXCL11 were associated with SAR. We identified 14 genes associated with atopy. We organized the Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. With a high-density single-nucleotide-polymorphism genotyping assay, we perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. We found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 and suggestive evidence of linkage to 14q11.2, 14q11.2-q13.2, and 20p12.1-p11.2. Less

Report

(6 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (49 results)

All 2005 2004 Other

All Journal Article (20 results) Patent(Industrial Property Rights) (2 results) Publications (27 results)

  • [Journal Article] Positional Identification of an Asthma Susceptibility Gene on Human Chromosome 5q332005

    • Author(s)
      Noguchi E, Yokouchi Y, Zhang J, Shibuya K, Shibuya A, Bannai M, Tokunaga K, Doi H, Tamari M, Shimizu M, Shirakawa T, Shibasaki M, Ichikawa K, Arinami T
    • Journal Title

      American Journal of Respiratory Critical Care Medicine 172

      Pages: 183-188

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Haplotype analysis of a 100 kb region spanning TNF-LTA identifies a polymorphism in the LTA promoter region that is associated with atopic asthma susceptibility in Japan2005

    • Author(s)
      Migita O, Noguchi E, Koga M, Jian Z, Shibasaki M, Migita T, Ito S, Ichikawa K, Matsui A, Arinami T
    • Journal Title

      Clinical Experimental Allergy 35

      Pages: 790-796

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of a haplotype block spanning SDAD1 gene and CXC chemokine genes with allergic rhinitis2005

    • Author(s)
      Zhang J, Noguchi E, Migita O, Yokouchi Y, Nakayama J, Shibasaki M, Arinami T
    • Journal Title

      Journal of Allergy and Clinical Immunology 115

      Pages: 548-554

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p2005

    • Author(s)
      Arinami T, Ohtsuki T, Ishiguro H, Ujike H, Tanaka Y, Morita Y, Mineta M, Takeichi M, Yamada S, Imamura A, Ohara K, Shibuya H, Ohara K, Suzuki Y, Muratake T, Kaneko N, Someya T, Inada T, Yoshikawa T, Toyota T, Yamada K, Kojima T, Takahashi S, Osamu O, Shinkai T, Nakamura M, Fukuzako H, Hashiguchi T, Niwa SI, Ueno T, Tachikawa H, Hori T, Asada T, Nanko S, Kunugi H, Hashimoto R, Ozaki N, Iwata N, Harano M, Arai H, Ohnuma T, Kusumi I, Koyama T, Yoneda H, Fukumaki Y, Shibata H, Kaneko S, Higuchi H, Yasui-Furukori N, Numachi Y, Itokawa M, Okazaki Y; Japanese Schizophrenia Sib-Pair Linkane Group
    • Journal Title

      American Journal of Human Genetics. 77(6) : 937-944, 2005 77

      Pages: 937-944

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Positional Identification of an Asthma Susceptibility Gene on Human Chromosome 5q33.2005

    • Author(s)
      Noguchi E, Yokouchi Y, Zhang J, Shibuya K, Shibuya A, Bannai M, Tokunaga K, Doi H, Tamari M, Shimizu M, Shirakawa T, Shibasaki M, Ichikawa K, Arinami T
    • Journal Title

      American Journal of Respiratory Critical Care Medicine. 172(2)

      Pages: 183-188

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Haplotype analysis of a 100 kb region spanning TNF-LTA identifies a polymorphism in the LTA promoter region that is associated with atopic asthma susceptibility in Japan.2005

    • Author(s)
      Migita O, Noguchi E, Koga M, Jian Z, Shibasaki M, Migita T, Ito S, Ichikawa K, Matsui A, Arinami T
    • Journal Title

      Clinical Experimental Allergy. 35(6)

      Pages: 90-796

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of a haplotype block spanning SDAD1 gene and CXC chemokine genes with allergic rhinitis.2005

    • Author(s)
      Zhang J, Noguchi E, Migita O, Yokouchi Y, Nakayama J, Shibasaki M, Arinami T
    • Journal Title

      Journal of Allergy and Clinical Immunology 115(3)

      Pages: 548-554

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.2005

    • Author(s)
      Arinami T, Ohtsuki T, Ishiguro H, Ujike H, Tanaka Y, Morita Y, Mineta M, Takeichi M, Yamada S, Imamura A, Ohara K, Shibuya H, Ohara K, Suzuki Y, Muratake T, Kaneko N, Someya T, Inada T, Yoshikawa T, Toyota T, Yamada K, Kojima T, Takahashi S, Osamu O, Shinkai T, Nakamura M, Fukuzako H, Hashiguchi T, Niwa SI, Ueno T, Tachikawa H, Hori T, Asada T, Nanko S, Kunugi H, Hashimoto R, Ozaki N, Iwata N, Harano M, Arai H, Ohnuma T, Kusumi I, Koyama T, Yoneda H, Fukumaki Y, Shibata H, Kaneko S, Higuchi H, Yasui-Furukori N, Numachi Y, Itokawa M, Okazaki Y ; Japanese Schizophrenia Sib-Pair Linkage Group
    • Journal Title

      American Journal of Human Genetics. 77(6)

      Pages: 937-944

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of a haplotype block spanning SDAD1 gene and CXC chemokine genes with allergic rhinitis2005

    • Author(s)
      Noguchi E, Arinami T 他
    • Journal Title

      J Allergy Clin Immunol. 115・3

      Pages: 548-554

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Associations between serum high-density lipoprotein cholesterol or apolipoprotein AI levels and common genetic variants of the ABCA1 gene in Japanes school-aged children2004

    • Author(s)
      Yamakawa-Kobayashi K, Yanagi H, Yu Y, Endo K, Arinami T, Hamaguchi H
    • Journal Title

      Metabolism 53

      Pages: 182-186

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An association study of asthma and total serum IgE levels for Toll-like receptors polymorphisms in the Japanese population2004

    • Author(s)
      Noguchi E, Nishimura F, Fukai H, Kim JE, Ichikawa K, Shibasaki M, Arinami T
    • Journal Title

      Clinical and Experimental Allergy 34

      Pages: 177-183

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association between a polymorphism in cysteinyl leukotriene receptor 2 on chromosome 13q14 and atopic asthma2004

    • Author(s)
      Fukai H, Ogasawara Y, Migita O, Koga M, Ichikawa K, Shibasaki M, Arinami T, Noguchi E
    • Journal Title

      Pharmacogenetics 14

      Pages: 683-690

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Associations between serum high-density lipoprotein cholesterol or apolipoprotein AI levels and common genetic variants of the ABCA1 gene in Japanese school-aged children2004

    • Author(s)
      Yamakawa-Kobayashi K, Yanagi H, Yu Y, Endo K, Arinami T, Hamaguchi H
    • Journal Title

      Metabolism 53(2)

      Pages: 182-186

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An association study of asthma and total serum IgE levels for Toll-like receptors polymorphisms in the Japanese population.2004

    • Author(s)
      Noguchi E, Nishimura F, Fukai H, Kim JE, Ichikawa K, Shibasaki M, Arinami T
    • Journal Title

      Clinical and Experimental Allergy 34(2)

      Pages: 177-183

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association between a polymorphism in cysteinyl leukotriene receptor 2 on chromosome 13q14 and atopic asthma.2004

    • Author(s)
      Fukai H, Ogasawara Y, Migita O, Koga M, Ichikawa K, Shibasaki M, Arinami T, Noguchi E
    • Journal Title

      Pharmacogenetics 14(10)

      Pages: 683-690

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Associations between serum high-density lipoprotein cholesterol or apolipoprotein AI levels and common genetic variants of the ABCA1 gene in Japanese school-aged children.2004

    • Author(s)
      Yamakawa-Kobayashi, Arinami T 他
    • Journal Title

      Metabolism 53・2

      Pages: 182-186

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ADRB2 polymorphisms and asthma susceptibility : transmission disequilibrium test and meta-analysis2004

    • Author(s)
      Noguchi E, Arinami T 他
    • Journal Title

      Int Arch Allergy Immunol. 134・2

      Pages: 150-157

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Association between chromogranin b gene polymorphisms and schizophrenia in the Japanese population2004

    • Author(s)
      Ohtsuki T, Arinami T 他
    • Journal Title

      Biol Psychiatry 56・1

      Pages: 10-17

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Failure to confirm association between AKT1 haplotype and schizophrenia in a Japanese case-control population2004

    • Author(s)
      Ohtsuki T, Arinami T 他
    • Journal Title

      Mol Psychiatry 9・11

      Pages: 981-983

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Association between a polymorphism in cysteinyl leukotriene receptor 2 on chromosome 13q14 and atopic asthma.2004

    • Author(s)
      Noguchi E, Arinami T 他
    • Journal Title

      Pharmacogenetics. 14・10

      Pages: 683-690

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 喘息および/またはアレルギー性鼻炎の素因の評価法2004

    • Inventor(s)
      有波忠雄, 野口恵美子
    • Industrial Property Rights Holder
      有波忠雄, 野口恵美子
    • Filing Date
      2004-09-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 喘息および/またはアレルギー性鼻炎の素因の評価法2004

    • Inventor(s)
      有波 忠雄, 野口 恵美子
    • Industrial Property Rights Holder
      有波 忠雄, 野口 恵美子
    • Filing Date
      2004-09-07
    • Related Report
      2004 Annual Research Report
  • [Publications] Noguchi E, Arinami T 他: "The promoter polymorphism in the eosinophil cationic protein gene and its influence on the serum eosinophil cationic protein level."American Journal of Respiratory and Critical Care Medicine. 167(2). 180-184 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Noguchi E, Arinami T 他: "Insertion/deletion coding polymorphisms in hHAVcr-1 are not associated with atopic asthma in the Japanese population"Genes and Immunity. 4(2). 170-173 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Noguchi E, Arinami T 他: "Association between polymorphisms in the SPINK5 gene and atopic dermatitis in the Japanese"Genes and Immunity. 4(7):. 515-517 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Noguchi E, Arinami T 他: "No evidence for association between the -112G/A polymorphism of UGRP1 and childhood atopic asthma"Clinical and Experimental Allergy. 33(7):. 902-904 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Noguchi E, Arinami T 他: "An association study of asthma and total serum IgE levels for Toll-like receptors polymorphisms in the Japanese population"Clinical and Experimental Allergy. 4(7). 515-517 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Noguchi E, Arinami T 他: "An association study of asthma and total serum IgE levels for Toll-like receptors polymorphisms in the Japanese population"Clinical and Experimental Allergy. 34(2). 177-183 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 有波忠雄: "新規抗精神病薬のすべて"先端医学社. 293 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Noguchi E, Arinami T et al.: "Association between TNFA polymorphism and the development of asthma in the Japanese population"American Journal of Respiratory and Critical Care Medicine. 166(1). 43-46 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yokouchi Y, Arinami T et al.: "A genome-wide linkage analysis of orchard-grass-sensitive childhood seasonal allergic rhinitis in Japanese families"Genes and Immunity. 3(1). 9-13 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noguchi E, Arinami T et al.: "Insertion/deletion coding polymorphisms in hHAVcr-1 are not associated with atopic asthma in the Japanese population"Genes and Immunity. 4(2). 170-173 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noguchi E, Arinami T et al.: "The promoter polymorphism in the eosinophil cationic protein gene and its influence on the serum eosinohil cationic protein level"American Journal of Respiratory and Critical Care Medicine. 167(2). 180-184 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arinami et al.: "Initial genome-wide scan for linkage with schizophrenia in the Japanese Schizophrenia Sib-pair Linkage Group(JSSLG)families"American Journal of Medical Genetics. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi S, Arinami T et al.: "Significant Linkage to Chromosome 22q for Exploratory Eye Movement Dysfunction in Schizophrenia"American Journal of Medical Genetics. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Noguchi E, Shibasaki M, Arinami T 他: "Association between a new polymorphism of the Activation-induced Cytidine Deaminase (AICDA) and total serum IgE level"J Allergy and Clinical Immunology. 108・3. 382-386 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noguchi E, Shibasaki M, Arinami T 他: "Haplotypes of the 5' region of the IL-4 gene and SNPs in the intergene sequence between the IL-4 and IL-13 genes are associated with atopic asthma"Human Immunology. 62・11. 1251-1257 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noguchi E, Shibasaki M, Arinami T 他: "Identification of missense mutation in the IL12B gene : lack of association between IL12B polymorphisms and asthma and allergic rhinitis in the Japanese population"Genes and Immunology. 2・7. 401-403 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishio Y, Noguchi E, Arinami T 他: "Mutation and association analysis of the interferon regulatory factor 2 gene (IRF2) with atopic dermatitis"Journal of Human Genetics. 46・11. 664-667 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Arinami T 他: "Screening for 22q11 deletions in a schizophrenia population"Schizophrenia Research. 52・3. 167-170 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohtsuki T, Arinami T 他: "Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia"Molecular Psychiatry. 6・2. 211-216 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakurai K: "Mutation analysis of the N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia."Neurosci lett. 296. 168-170 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishiguro H: "Mutation and association analysis of the 5' region of the dopamine D3 receptor gene in schizophrenia patients : identification of the Ala38Thr polymorphism and suggested association between DRD3 haplotypes and schizophrenia"Mol Psychiatry. 5. 433-438 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohtsuki T: "Mutational analysis of the synapsin III gene on chromosome 22q12-q13 in schizophrenia.94:1-7,2000"Psychiatry Res. 94. 1-7 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Noguchi E: "Mutation screening of Interferon regulatory factor 1 gene (IRF-1) as a candidate gene for asthma.30:,2000"Clin Exp Allergy. 30. 1563-1567 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tokouchi,Y.,: "Significant Evidence for Linkage of Mite-Sensitive Childhood Asthma to Chromosome 5q31-q33 near the Interleukin 12 B Locus by a Genome-wide Search in Japanese Families"Genomics. 66. 152-160 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kimura K: "Linkage and association of atopic asthma to markers on chromosome 13 in the Japanese population"Hum Mol Genet. 8. 1487-1490 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 有波忠雄: "遺伝と疾患"岩波書店. 12 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 有波忠雄: "臨床精神医学講座24"中山書店. 11 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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