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Genome-wide association study for rheumatoid arthritis using a large prospective cohort: a pilot study for personalized medicine.

Planned Research

Project AreaImmunological Self Recognition and its Disorders
Project/Area Number 22021023
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

MATSUDA Fumihiko  京都大学, 大学院・医学研究科, 教授 (50212220)

Co-Investigator(Renkei-kenkyūsha) YAMANAKA Hisashi  東京女子医科大学, 医学部, 教授 (10166754)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 2011: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2010: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywords関節リウマチ / 生物学的製剤 / 一塩基多型 / ゲノムワイド関連解析 / 薬剤感受性遺伝子
Research Abstract

We have established a national consortium for rheumatic disease study (GARNET Consortium) and accumulated more than 10,000 DNA samples of Japanese rheumatoid arthritis (RA) patients for genetic studies. We conducted a mata-analysis of genome-wide association (GWA) studies and newly identified 12 gene loci associated with RA in Japanese. We then investigated the biological role of myelin basic protein (MBP) gene, one of the above 12 genes, and found that autoantibodies against MBP were significantly increased in patients with RA beyond ethnicity, suggesting its usefulness as a diagnostic marker. We also found that multiple HLA-DRB1 alleles are associated with ACPA-negative rheumatoid arthritis in Japanese subjects. We have collected DNA samples of 299 RA patients treated with tocilizumab, biologic agent against interleukin 6 receptor, of which 120 DNA samples were subjected to the GWA study. Thirty-five candidate regions were identified, and the results are under confirmation with the other DNA samples.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Products Report
  • Research Products

    (26 results)

All 2014 2012 2011 2010 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (6 results) Remarks (1 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 1 results)

  • [Journal Article] Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population2012

    • Author(s)
      Okada, Y., Terao, C., Ikari, K., Kochi, Y., Ohmura, K., Suzuki, A., Kawaguchi, T., Stahl, E.A., Kurreeman, F.A., Nishida, N., Ohmiya, H., Myouzen, K., Takahashi, M., Sawada, T., Nishioka, Y., Yukioka, M., Matsubara, T., Wakitani, S., Teshima, R., Tohma, S., Takasugi, K., Shimada, K., Murasawa, A., Honjo, S., Matsuo, K., Tanaka, H., Tajima, K., Suzuki, T., Iwamoto, T., Kawamura, Y., Tanii, H., Okazaki, Y., Sasaki, T., Gregersen, P.K., Padyukov, L., Worthington, J., Siminovitch, K.A., Lathrop, M., Taniguchi, A., Takahashi, A., Tokunaga, K., Kubo, M., Nakamura, Y., Kamatani, N., Mimori, T., Plenge, R.M., Yamanaka, H., Momohara, S., Yamada, R., Matsuda, F., and Yamamoto, K.
    • Journal Title

      Nat. Genet.

      Volume: 44 Pages: 511-516

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative effect of HLA-DRB1 alleles to ACPA levels in Japanese rheumatoid arthritis: no strong genetic impact of shared epitope to ACPA levels after stratification of HLA-DRB12012

    • Author(s)
      Terao, C., Ikari, K., Ohmura, K., Suzuki, T., Iwamoto, T., Takasugi, K., Saji, H., Taniguchi, A., Momohara, S., Yamanaka, H., Matsuda, F., and Mimori, T.
    • Journal Title

      Ann Rheum Dis.

      Volume: 71 Pages: 1095-1097

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A trans-ethnic genetic study of rheumatoid arthritis identified FCGR2A as a candidate common risk factor in Japanese and European populations2012

    • Author(s)
      Meziani R., et al
    • Journal Title

      Modern Rheumatology

      Volume: 22 Issue: 1 Pages: 52-58

    • DOI

      10.1007/s10165-011-0467-y

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese2012

    • Author(s)
      岡田随象
    • Journal Title

      PLoS Genetics

      Volume: (掲載確定) Issue: 1 Pages: 1002455-1002455

    • DOI

      10.1371/journal.pgen.1002455

    • NAID

      120005906866

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The human AIRE gene at chromosome 21q22 is a genetic determinant for the predisposition to rheumatoid arthritis in Japanese population2011

    • Author(s)
      Terao, C., Yamada, R., Ohmura, K., Takahashi, M., Kawaguchi, T., Kochi, Y.; Human Disease Genomics Working Group; Rheumatoid Arthritis (RA) Clinical and Genetic Study Consortium, Okada, Y., Nakamura, Y., Yamamoto, K., Melchers, I., Lathrop, M., Mimori, T., and Matsuda, F.
    • Journal Title

      Hum. Mol. Genet.

      Volume: 20 Pages: 2680-265

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Myelin basic protein as a novel genetic risk factor in rheumatoid arthritis-a genome-wide study combined with immunological analyses2011

    • Author(s)
      Terao, C., Ohmura, K., Katayama, M., Takahashi, M., Kokubo, M,, Diop, G., Toda, Y., Yamamoto, N; Human Disease Genomics Working Group; Rheumatoid Arthritis (RA) Clinical and Genetic Study Consortium, Shinkura, R., Shimizu, M., Gut, I., Heath, S., Melchers, I., Manabe, T., Lathrop, M., Mimori, T., Yamada, R. and Matsuda F.
    • Journal Title

      PLoS One

      Volume: 6

    • NAID

      120003184064

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A large-scale association study identified multiple HLA-DRB1 alleles associated with ACPA-negative rheumatoid arthritis in Japanese subjects2011

    • Author(s)
      Terao, C., Ohmura, K., Kochi, Y., Ikari, K., Maruya, E., Katayama, M., Shimada, K., Murasawa, A., Honjo, S., Takasugi, K., Matsuo, K., Tajima, K., Suzuki, A., Yamamoto, K., Momohara, S., Yamanaka, H., Yamada, R., Saji, H., Matsuda, F. and Mimori, T.
    • Journal Title

      Ann Rheum Dis

      Volume: 70 Pages: 2134-9

    • NAID

      120003796492

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The human AIRE gene at chromosome 21q22 is a genetic determinant for the predisposition to rheumatoid arthritis in Japanese population2011

    • Author(s)
      Terao C, et al
    • Journal Title

      Human Molecular Genetics

      Volume: 20 Issue: 13 Pages: 2680-2685

    • DOI

      10.1093/hmg/ddr161

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Myelin basic protein as a novel genetic risk factor in rheumatoid arthritis-a genome-wide study combined with immunological analyses2011

    • Author(s)
      Terao C., et at
    • Journal Title

      PLoS ONE

      Volume: 6 Issue: 6 Pages: e20457-e20457

    • DOI

      10.1371/journal.pone.0020457

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interferon-gamma release assay for diagnosing Mycobacterium tuberculosis infections in patients with systemic lupus erythematosus2011

    • Author(s)
      Takeda N., et al
    • Journal Title

      Lupus

      Volume: 20 Issue: 8 Pages: 792-800

    • DOI

      10.1177/0961203310397966

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A large-scale association study identified multiple HLA-DRB1 alleles associated with ACPA-negative rheumatoid arthritis in Japanese subjects2011

    • Author(s)
      Terao C, Ohmura K, Kochi Y, Ikari K, et al
    • Journal Title

      Annals of the rheumatic diseases

      Volume: 70 Issue: 12 Pages: 2134-9

    • DOI

      10.1136/annrheumdis-2011-200353

    • NAID

      120003796492

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility2010

    • Author(s)
      Kochi, Y., Okada, Y., Suzuki, A., Ikari, K., Terao, C., Takahashi, A., Yamazaki, K., Hosono, N., Myouzen, K., Tsunoda, T., Kamatani, N., Furuichi, T., Ikegawa, S., Ohmura, K., Mimori, T., Matsuda, F., Iwamoto, T., Momohara, S., Yamanaka, H., Yamada, R., Kubo, M., Nakamura, Y., and Yamamoto, K.
    • Journal Title

      Nat. Genet.

      Volume: 42 Pages: 515-519

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-citrullinated peptide antibody-negative RA is a genetically distinct subset: a definitive study using only bone-erosive ACPA-negative rheumatoid arthritis2010

    • Author(s)
      Ohmura, K., Terao, C., Maruya, E., Katayama, M., Matoba, K., Shimada, K., Murasawa, A., Honjo, S., Takasugi, K., Tohma, S., Matsuo, K., Tajima, K., Yukawa, N., Kawabata, D., Nojima, T., Fujii, T., Yamada, R., Saji, H., Matsuda, F., and Mimori, T.
    • Journal Title

      Rheumatol.

      Volume: 49 Pages: 2298-2304

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility.2010

    • Author(s)
      高地雄太
    • Journal Title

      Nature Genetics

      Volume: 42 Pages: 515-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-citrullinated peptide antibody-negative RA is a genetically distinct subset : a definitive study using only bone-erosive ACPA-negative rheumatoid arthritis.2010

    • Author(s)
      大村浩一郎
    • Journal Title

      Rheumatology (Oxford)

      Volume: 49 Pages: 2298-304

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] A large-scale association study identified multiple HLA-DRB1 alleles associated with anti-citrullinated peptide antibody negative rheumatoid arthritis in Japanese2011

    • Author(s)
      Terao Chikashi et al.
    • Organizer
      Annual Congress of American College of Rheumatology
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2011-11-06
    • Related Report
      2011 Final Research Report
  • [Presentation] A large-scale association study identihed multiple HLA-DRB1 alleles associated with anti-citrullinated peptide antibody negative rheumatoid arthritis in Japanese2011

    • Author(s)
      Chikashi Terao., et at
    • Organizer
      アメリカリウマチ学会
    • Place of Presentation
      McCormick Place Chicago USA
    • Year and Date
      2011-11-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] 関節リウマチの病型と疾患感受性遺伝子、及びその機能解析2011

    • Author(s)
      寺尾知可史
    • Organizer
      日本臨床免疫学会
    • Place of Presentation
      京王プラザホテル東京(招待講演)
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 抗CCP抗体陰性関節リウマチ関連HLA-DRB1アレルおよびディプロタイプの同定2011

    • Author(s)
      寺尾知可史, 他
    • Organizer
      日本臨床免疫学会
    • Place of Presentation
      京王プラザホテル東京
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] A haplotype of the human AIRE gene is associated with the risk for rheumatoid arthritis in Japanese population2011

    • Author(s)
      Terao Chikashi et al.
    • Organizer
      EULAR Congress 2011
    • Place of Presentation
      London, UK
    • Year and Date
      2011-05-27
    • Related Report
      2011 Final Research Report
  • [Presentation] A haplotype of the human AIRE gene is associated with the risk for rheumatoid arthritis in Japanese population2011

    • Author(s)
      Chikashi Terao., et al
    • Organizer
      ヨーロッパリウマチ学会
    • Place of Presentation
      EXCEL London UK
    • Year and Date
      2011-05-27
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.genome.med.kyoto-u.ac.jp/index.html

    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 関節リウマチの新規遺伝因子としてのミエリン塩基性蛋白の利用2014

    • Inventor(s)
      松田文彦、三森経世、大村浩一郎、寺尾知可史
    • Industrial Property Rights Holder
      国立大学法人 京都大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-06-09
    • Acquisition Date
      2017-04-21
    • Related Report
      Products Report
  • [Patent(Industrial Property Rights)] 関節リウマチの新規遺伝因子としてのミエリン塩基性蛋白の利用2011

    • Inventor(s)
      松田文彦, 三森経世, 大村浩一郎, 寺尾知可史
    • Industrial Property Rights Holder
      京都大学
    • Filing Date
      2011-04-01
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 関節リウマチの新規遺伝因子としてのミェリン塩基性蛋白の利用2011

    • Inventor(s)
      松田文彦, 三森経世, 大村浩一郎, 寺尾知可史
    • Industrial Property Rights Holder
      京都大学
    • Filing Date
      2011-04-01
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 関節リウマチの新規遺伝因子としてのミェリン塩基性蛋白の利用2011

    • Inventor(s)
      松田文彦, 三森経世, 大村浩一郎, 寺尾知可史
    • Industrial Property Rights Holder
      京都大学
    • Filing Date
      2011-04-01
    • Related Report
      2011 Annual Research Report
    • Overseas

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Published: 2010-08-23   Modified: 2019-02-27  

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