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A genome-wide association study in Japanese patients with rheumatoid arthritis in order to identify susceptibility loci for Methotrexate-associated lymphoproliferative disorder.

Research Project

Project/Area Number 20H03722
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionTokyo Women's Medical University

Principal Investigator

Harigai Masayoshi  東京女子医科大学, 医学部, 教授 (20238207)

Co-Investigator(Kenkyū-buntansha) 高地 雄太  東京医科歯科大学, 難治疾患研究所, 教授 (60415156)
猪狩 勝則  東京女子医科大学, 医学部, 特任教授 (80343557)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Keywords関節リウマチ / リンパ腫 / 遺伝子 / メトトレキサート関連リンパ腫 / ゲノムワイド関連解析 / メトトレキサート関連リンパ増殖性疾患 / 関連遺伝子 / MTX-LPD / メトトレキサート
Outline of Research at the Start

近年、関節リウマチにおける重篤な合併症の一つとしてMTX投与中に発生するMTX関連リンパ増殖性疾患(Methotrexate-associated lymphoproliferative disorder, MTX-LPD)が注目されている。本研究の目的は網羅的な遺伝子解析によりMTX-LPDの遺伝的危険因子を同定することである。

Outline of Final Research Achievements

Aggressive immunosuppressive therapy is often required for the treatment of rheumatoid arthritis, and methotrexate (MTX) is used as an anchor drug. Recently, MTX-associated lymphoproliferative disorder (MTX-LPD), which occurs during MTX administration, has attracted attention as a serious complication. In this study, we collected samples and performed a comprehensive genetic analysis with the aim of identifying genetic risk factors for MTX-LPD. Unfortunately, we were not able to identify significant genetic risk factors, but our findings are useful for future research.

Academic Significance and Societal Importance of the Research Achievements

関節リウマチの治療における第一選択薬であるメトトレキサート(MTX)の重篤な合併症の1つに、MTX関連リンパ増殖性疾患(MTX-LPD)があげられる。本研究ではMTX-LPDの遺伝的危険因子を同定することを目的に、試料収集、網羅的な遺伝子解析を行った。残念ながら検定力の不足により、有意な遺伝的危険因子の同定には至らなかったものの、今後も試料収集を続けることで将来的にはその同定の可能性が高いと考えられた。また多くの患者試料で得られた全ゲノム領域の遺伝子多型同定の結果は他の関節リウマチ関連遺伝子解析にも役立てることが可能である。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (6 results)

All 2023 2022

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results)

  • [Journal Article] Risk of hospitalized infections in older elderly patients with rheumatoid arthritis treated with tocilizumab or other biological/targeted synthetic disease-modifying antirheumatic drugs: Evaluation of data from a Japanese claims database2023

    • Author(s)
      Harigai Masayoshi、Fujii Takao、Sakai Ryoko、Igarashi Ataru、Shoji Ayako、Yamaguchi Hiroko、Iwasaki Katsuhiko、Makishima Misako、Yoshida Amika、Okada Norihiro、Yamashita Katsuhisa、Kawahito Yutaka
    • Journal Title

      Modern Rheumatology

      Volume: - Issue: 2 Pages: 287-296

    • DOI

      10.1093/mr/road031

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Association of HLA class II alleles with risk of relapse in myeloperoxidase-antineutrophil cytoplasmic antibody positive vasculitis in the Japanese population.2023

    • Author(s)
      Kawasaki A, Sada K-e, Kusumawati PA, Hirano F, Kobayashi S, Nagasaka K, Sugihara T, Ono N, Fujimoto T, Kusaoi M, Tamura N, Kusanagi Y, Itoh K, Sumida T, Yamagata K, Hashimoto H, Makino H, Arimura Y, Harigai M, Tsuchiya N
    • Journal Title

      Frontiers in Immunology

      Volume: 14 Pages: 1119064-1119064

    • DOI

      10.3389/fimmu.2023.1119064

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nationwide clinical and epidemiological study of large-vessel vasculitis in Japan in 20172023

    • Author(s)
      Konda Naoko、Sakai Ryoko、Saeki Keigo、Matsubara Yuri、Nakamura Yosikazu、Miyamae Takako、Nakaoka Yoshikazu、Harigai Masayoshi
    • Journal Title

      Modern Rheumatology

      Volume: - Issue: 1 Pages: 167-174

    • DOI

      10.1093/mr/road019

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Late-onset rheumatoid arthritis registry study, LORIS study: study protocol and design.2022

    • Author(s)
      Kojima M, Kawahito Y, Sugihara T, Kojima T, Harada R, Hirata S, Hashimoto M, Hidaka T, Ishikawa H, Ito H, Kishimoto M, Kaneko Y, Matsui K, Matsui T, Matsushita I, Morinobu A, Nishida K, Tanaka E, Abe A, Ishitoku M, Asai S, Kida T, Onishi A, Takanashi S, Harigai M.
    • Journal Title

      BMC Rheumatol.

      Volume: 6 (1) Issue: 1 Pages: 90-90

    • DOI

      10.1186/s41927-022-00322-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis2022

    • Author(s)
      Ishigaki K, Sakaue S, Terao C, Luo Y, Sonehara KvYamaguchi K, Amariuta T, Too CL, Laufer VA, Scott IC, Viatte S, Takahashi M, Ohmura K, Murasawa A, Hashimoto M, Ito H, ..., Okada Y et al.
    • Journal Title

      Nature Genetics

      Volume: 54 Issue: 11 Pages: 1640-1651

    • DOI

      10.1038/s41588-022-01213-w

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of Polygenic Risk Scores With Radiographic Progression in Patients With Rheumatoid Arthritis2022

    • Author(s)
      Honda Suguru、Ikari Katsunori、Yano Koichiro、Terao Chikashi、Tanaka Eiichi、Harigai Masayoshi、Kochi Yuta
    • Journal Title

      Arthritis & Rheumatology

      Volume: - Issue: 5 Pages: 791-800

    • DOI

      10.1002/art.42051

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed

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Published: 2020-04-28   Modified: 2024-01-30  

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