• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Pharmacogenetic study of methotrexate in patients with rheumatoid arthritis.

Research Project

Project/Area Number 26461477
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionToho University

Principal Investigator

KAWAI Shinichi  東邦大学, 医学部, 教授 (70129401)

Co-Investigator(Kenkyū-buntansha) 山本 竜大  東邦大学, 医学部, 助教 (40459805)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsメトトレキサート / 関節リウマチ / 細胞内代謝 / 遺伝子多型 / 薬理遺伝学 / 民族差
Outline of Final Research Achievements

Methotrexate (MTX) is an essential drug for treatment of rheumatoid arthritis (RA). However, the response and tolerability to this drug is known to vary among patients and ethnics. In fact, MTX doses in clinical settings were approximately 7-9 mg/week and >15 mg/week in Japanese and Caucasian RA patients, respectively. We then focused to the intracellular polyglutamates (PGs) of MTX in patients with RA. Efficiency of PGs was lower in patients with MTX adverse events. Genotypes of folylpolyglutamate synthase (FPGS) significantly influenced to the concentration of MTXPGs, resulting in the increased efficiency of PGs in a Caucasian population when compared to our Japanese RA patients.
In conclusion, differences in allele frequencies of FPGS gene between different ethnic populations may suggest the significant differences in tolerable doses to MTX between these cohorts. (Appeared in Sci Rep. 6, 35615)

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (19 results)

All 2016 2015 2014 Other

All Journal Article (9 results) (of which Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Invited: 5 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Serum resistin level and progression of atherosclerosis during glucocorticoid therapy for systemic autoimmune diseases.2016

    • Author(s)
      Tanaka N, Masuoka S, Kusunoki N, Nanki T, Kawai S.
    • Journal Title

      Metabolites.

      Volume: 6 Issue: 3 Pages: 28-28

    • DOI

      10.3390/metabo6030028

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Folylpolyglutamate synthase is a major determinant of intracellular methotrexate polyglutamates in patients with rheumatoid arthritis.2016

    • Author(s)
      Yamamoto T, Shikano K, Nanki T, Kawai S.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 149-150

    • DOI

      10.1038/srep35615

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Apparent hypothalamic-pituitary-adrenal axis suppression via reduction of interleukin-6 by glucocorticoid therapy in systemic autoimmune diseases.2016

    • Author(s)
      Fujio N, Masuoka S, Shikano K, Kusunoki N, Nanki T, Kawai S.
    • Journal Title

      PLoS ONE.

      Volume: 11 Issue: 12 Pages: e0167854-e0167854

    • DOI

      10.1371/journal.pone.0167854

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of vitamin K2 for glucocorticoid-induced osteoporosis in patients with systemic autoimmune diseases.2016

    • Author(s)
      Shikano K, Kaneko K, Kawazoe M, Kaburaki M, Hasunuma T, Kawai S.
    • Journal Title

      Internal Medicine

      Volume: in press

    • NAID

      130005254821

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Absence of ethnic differences in the pharmacokinetics of moxifloxacin, simvastatin, and meloxicam among three east Asian populations and Caucasians.2016

    • Author(s)
      Hasunuma T, Tohkin M, Kaniwa N, Jang IJ, Cui Y, Kaneko M, Saito Y, Takeuchi M, Watanabe H, Yamazoe Y, Uyama Y, Kawai S.
    • Journal Title

      British Journal of Clinical Pharmacology

      Volume: in press Issue: 6 Pages: 1078-1090

    • DOI

      10.1111/bcp.12884

    • Related Report
      2015 Research-status Report
    • Open Access
  • [Journal Article] The growth factor midkine may play a pathophysiological role in rheumatoid arthritis.2016

    • Author(s)
      Shindo E, Nanki T, Kusunoki N, Shikano K, Kawazoe M, Sato H, Kaneko K, Muraoka S, Kaburaki M, Akasaka Y, Shimada H, Hasunuma T, Kawai S.
    • Journal Title

      Modern Rheumatology

      Volume: in press

    • Related Report
      2015 Research-status Report
  • [Journal Article] Pharmacokinetics, efficacy and safety profiles of etanercept monotherapy in Japanese patients with rheumatoid arthritis: review of seven clinical trials.2015

    • Author(s)
      Takeuchi T, Miyasaka N, Kawai S, Sugiyama N, Yuasa H, Yamashita N, Sugiyama N, Wagerle LC, Vlahos B, Wajdula J
    • Journal Title

      Modern Rheumatology

      Volume: 25 Issue: 2 Pages: 173-186

    • DOI

      10.3109/14397595.2014.914014

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Longterm Safety and Efficacy of Subcutaneous Tocilizumab Monotherapy: Results from the 2-year Open-label Extension of the MUSASHI Study.2015

    • Author(s)
      Ogata A, Amano K, Dobashi H, Inoo M, Ishii T, Kasama T, Kawai S, Kawakami A, Koike T, Miyahara H, Miyamoto T, Munakata Y, Murasawa A, Nishimoto N, Ogawa N, Ojima T, Sano H, Shi K, Shono E, Suematsu E, Takahashi H, Tanaka Y, Tsukamoto H, Nomura A and Investigators MS.
    • Journal Title

      The Journal of rheumatology

      Volume: 42 Issue: 5 Pages: 799-809

    • DOI

      10.3899/jrheum.140665

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] A feasibility study assessing tolerability of daily versus twice weekly trimethoprim-sulfamethoxazole regimen for prophylaxis against Pneumocystis pneumonia in patients with systemic autoimmune diseases on glucocorticoid therapy.2014

    • Author(s)
      Yamamoto T, Hasunuma T, Takagi K, Akimoto K, Shikano K, Kaburaki M, Muraoka S, Kitahara K, Tanaka N, Kaneko K, Kusunoki Y, Endo H, Kawai S.
    • Journal Title

      Jpn J Clin Pharmacol Ther.

      Volume: 45 Pages: 89-92

    • NAID

      130004679387

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 免疫・炎症・疼痛制御における臨床薬理学の進歩2016

    • Author(s)
      川合眞一
    • Organizer
      第37回日本臨床薬理学会学術総会
    • Place of Presentation
      米子コンベンションセンター(鳥取県米子市)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] バイオシミラー普及における臨床上の課題2016

    • Author(s)
      川合眞一
    • Organizer
      第6回レギュラトリーサイエンス学会学術大会
    • Place of Presentation
      一橋大学一橋講堂(東京都千代田区)
    • Year and Date
      2016-09-10
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ステロイドの使い方:臨床薬理と注意点2016

    • Author(s)
      川合眞一
    • Organizer
      第60回日本リウマチ学会総会・学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-04-22
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] いまどきのステロイド療法2014

    • Author(s)
      川合眞一
    • Organizer
      第24回日本リウマチ学会北海道・東北支部学術集会
    • Place of Presentation
      北海道大学医学部学友会館(北海道札幌市北区北15条西7丁目)
    • Year and Date
      2014-11-22
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Gamma-giutamyi hydrolase gene polymorphisms provide for intracellular methotrexate concentration on patients with rheumatoid arthritis.2014

    • Author(s)
      Kawai S, Yamamoto T
    • Organizer
      17th World Congress of Basic & Clinical Pharmacology
    • Place of Presentation
      The Cape Town International Convention Centre (Convention Square, 1 Lower Long Street, Cape Town, 8001, South Africa)
    • Year and Date
      2014-07-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 教育講演:DMARDsの適応と使い方2014

    • Author(s)
      川合眞一
    • Organizer
      第58回日本リウマチ学会総会・学術集会
    • Place of Presentation
      グランドプリンスホテル新高輪 国際館パミール(東京都港区高輪3-13-1)
    • Year and Date
      2014-04-24
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] メトトレキサート治療中の関節リウマチ患者における副作用の発現と、細胞内濃度および細胞内代謝関連酵素の遺伝子多型に関する研究2014

    • Author(s)
      藤尾夏樹,山本竜大,楠 夏子,増岡正太郎,川添麻衣,進藤恵美子,佐藤洋志,鹿野孝太郎,鏑木 誠,村岡 成,北原加奈子,田中菜穂子,金子開知,楠 芳恵,高木賢治,蓮沼智子,遠藤平仁,川合眞一
    • Organizer
      第58回日本リウマチ学会総会・学術集会
    • Place of Presentation
      グランドプリンスホテル新高輪 国際館パミール(東京都港区高輪3-13-1)
    • Year and Date
      2014-04-24
    • Related Report
      2014 Research-status Report
  • [Book] Arachidonic Acid: Sources, Biosynthesis and Health Effects.2014

    • Author(s)
      Kusunoki N, Kojima F, Kawai S.
    • Publisher
      Nova Science Publishers, Inc.
    • Related Report
      2014 Research-status Report
  • [Remarks] 東邦大学教育・研究業績データベース(2016年度 内科学講座膠原病学分野(大森))

    • URL

      http://gyoseki.toho-u.ac.jp/thuhp/KgApp?kozac=22010024&year=2016

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東邦大学医療センター大森病院リウマチ膠原病センター(膠原病科)教育・研究業績データベース

    • URL

      http://www.lab.toho-u.ac.jp/med/omori/kogen/research/achievement_db.html

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi