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The relationship between trichlormethiazide-induced hyperuricemia and the genotypes of uric acid transporters

Research Project

Project/Area Number 24390140
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionKyushu University

Principal Investigator

TOSHIYUKI Sasaguri  九州大学, 医学(系)研究科(研究院), 教授 (30261209)

Co-Investigator(Kenkyū-buntansha) MATSUMURA Kiyoshi  九州大学, 医学研究院, 准教授 (70285409)
TAKAHASHI Fumi  九州大学, 医学研究院, 講師 (50274436)
YOSHIHARA Tatsuya  九州大学, 医学研究院, 助教 (80419613)
松村 潔  九州大学, 医学(系)研究科(研究院), 准教授 (70285469)
Co-Investigator(Renkei-kenkyūsha) IKEMATU Hideyuki  久留米臨床薬理クリニック
OHTSUBO Toshio  九州大学, 病院, 講師 (30423974)
SHIRAISHI Fumie  九州大学, 医学研究院, 技術専門員
Research Collaborator ARIMA Hisatomi  滋賀医科大学, アジア疫学研究センター, 特任教授 (20437784)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywordsチアジド / 利尿薬 / 尿酸 / 遺伝子多型 / MRP4 / ABCC4 / BCRP / ABCG2 / 薬理ゲノム学 / 薬物トランスポーター / 高血圧 / 副作用 / ファーマコゲノミクス / トランスポーター
Outline of Final Research Achievements

Diuretics often cause hyperuricemia. Suppression of the function of urate transporter may be a mechanism of diuretics-induced hyperuricemia. In the present study, we examined whether genetic mutation of MRP4, BCRP, NPT4, URAT1 and GLUT9 influence serum uric acid (SUA) level and urinary urate excretion (UUE) after administration of trichlormethiazide (TCM).
MRP4 E757K polymorphism did not influence the increase of SUA after TCM treatment, although UUE was transiently reduced in subjects with EE genotype. The increase in SUA in subjects with QX genotype in BCRP Q126X polymorphism was larger than in those with QQ genotype. However, there was no difference in UUE between QQ and QX genotypes, indicating that TCM inhibited uric acid excretion into feces in subjects with QX genotype.
Our results suggest that the predominant mechanism of TCM-induced hyperuricemia may be the inhibition of intestinal BCRP.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (19 results)

All 2015 2014 2013 2012

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (15 results) (of which Invited: 1 results)

  • [Journal Article] Impact of antihypertensive medication adherence on blood pressure control in hypertension: the COMFORT study.2013

    • Author(s)
      Matsumura K, Arima H, Tominaga M, Ohtsubo T, Sasaguri T, Fujii K, Fukuhara M, Uezono K, Morinaga Y, Ohta Y, Otonari T, Kawasaki J, Kato I, Tsuchihashi T,; The Comfort Investigators
    • Journal Title

      QJM

      Volume: 106 Issue: 10 Pages: 909-914

    • DOI

      10.1093/qjmed/hct121

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide response to antihypertensive medication using home blood pressure measurements: A pilot study nested within the HOMED-BP study2013

    • Author(s)
      Kamide K, Asayama K, Katsuya T, Ohkubo T, Hirose T, Inoue R, Metoki H, Kikuya M, Obara T, Hanada H, Thijs L, Kuznetsova T, Noguchi Y, Sugimoto K, Ohishi M, Morimoto S, Nakahashi T, Takiuchi S, Ishimitsu T, Tsuchihashi T, Soma M, Higaki J, Matsuura H, Shinagawa T, Sasaguri T, Miki T, Takeda K, Shimamoto K, Ueno M, Hosomi N, Kato J, Komai N, Kojima S, Sase K, Miyata T, Tomoike H, Kawano Y, Ogihara T, Rakugi H, Staessen JA, Imai Y
    • Journal Title

      Pharmacogenomics

      Volume: 14 Issue: 14 Pages: 1709

    • DOI

      10.2217/pgs.13.161

    • URL

      https://pure.teikyo.jp/en/publications/c85d1b26-a0cb-42d3-89b0-92922a561e9f

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Does a Combination Pill of Antihypertensive Drugs Improve Medication Adherence in Japanese?2012

    • Author(s)
      Matsunura K, Arima H. Toninaga M, Ohtsubo T. Sasaguri T, Fujii K. Fukuhara M, Uezono K, Morinaga Y, Ohta Y Otonari T. Kavasaki J, Kato I, Tsuchihashi T for the COMFORT invest igators
    • Journal Title

      Circulation Journal

      Volume: 76 Issue: 6 Pages: 1415-1422

    • DOI

      10.1253/circj.CJ-11-1481

    • NAID

      10030316225

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of brain serotonin dysfunction in the pathophysiology of congestive heart failure2012

    • Author(s)
      Li L, Morimoto S, Take S, Zhan DY, Du CK Wang YY, Fan XL. Yoshihara T, Takahashi-Yanaga F, Katafuchi T, Sasaguri T
    • Journal Title

      J MoI Cell Cardiol

      Volume: 53 Pages: 760-767

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] The relationship between trichlormethiazide-induced hyperuricemia and the genotypes of uric acid transporters.2015

    • Author(s)
      Yoshihara T, Imai H, Shiraishi F, Sasaguri T
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] MRP4の遺伝子多型がトリクロルメチアジド投与後の血清尿酸値と尿酸クリアランスに及ぼす影響2014

    • Author(s)
      吉原達也、今井浩光、白石富美恵、有馬久富、高橋富美、池松秀之、小手川勤、笹栗俊之
    • Organizer
      第35回日本臨床薬理学会学術総会
    • Place of Presentation
      松山市
    • Year and Date
      2014-12-04 – 2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] MRP4の遺伝子多型がトリクロルメチアジド投与後の血清尿酸値および尿酸クリアランスに及ぼす影響に関する臨床試験2014

    • Author(s)
      吉原達也、有馬久富、笹栗俊之
    • Organizer
      第37回日本高血圧学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-10-17 – 2014-10-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Influence of a loss-of-function polymorphism of MRP4 on serum uric acid concentration and uric acid clearance after the administration of trichlormethiazide2014

    • Author(s)
      Tatsuya Yoshihara, Hiromitsu Imai, Fumie Shiraishi, Hisatomi Arima, Fumi Takahashi-Yanaga, Hideyuki Ikematsu, Tsutomu Kotegawa, Toshiyuki Sasaguri
    • Organizer
      17th World Congress of Basic and Clinical Pharmacology
    • Place of Presentation
      ケープタウン(南アフリカ共和国)
    • Year and Date
      2014-07-13 – 2014-07-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Influence of ALDH2 genotype on vascular endothelial function after a long-term treatment with glyceryl trinitrate2014

    • Author(s)
      吉原 達也、白石 富美恵、有馬 久富、高橋 富美、池松 秀之、笹栗 俊之
    • Organizer
      第87回 日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] ALDH2遺伝子多型がニトログリセリンの単回および長期投与効果に及ぼす影響に関する日本人健康成人を対象としたランダム化クロスオーバー試験2013

    • Author(s)
      吉原 達也、白石 富美恵、有馬 久富、高橋 富美、池松 秀之、笹栗 俊之
    • Organizer
      第32回 臨床薬理阿蘇九重カンファレンス
    • Place of Presentation
      松山
    • Related Report
      2013 Annual Research Report
  • [Presentation] 水中歩行の妊娠高血圧症候群予防効果に関する臨床研究2013

    • Author(s)
      吉原 達也、久保田 史郎、笹栗 俊之
    • Organizer
      第36回日本高血圧学会総会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] ALDH2遺伝子多型がニトログリセリン長期投与効果に及ぼす影響2013

    • Author(s)
      吉原 達也、白石 富美恵、有馬 久富、高橋 富美、池松 秀之、笹栗 俊之
    • Organizer
      第66回 日本薬理学会西南部会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] ロサルタン/ヒドロクロロチアジド合剤とロサルタン以外のアンジオテンシン受容体拮抗薬およびサイアザイド系利尿薬併用との比較:COMFORT試験2013

    • Author(s)
      有馬 久富、松村 潔、冨永 光裕、大坪 俊夫、笹栗 俊之、藤井 弘二、福原 正代、上園 慶子、守永 友希、大田 祐子、土橋 卓也、COMFORT試験グループ
    • Organizer
      第34回 日本臨床薬理学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] ALDH2遺伝子多型がニトログリセリンの単回および長期投与効果に及ぼす影響に関する日本人健康成人を対象としたランダム化クロスオーバー試験2013

    • Author(s)
      吉原 達也、白石 富美恵、有馬 久富、高橋 富美、池松 秀之、笹栗 俊之
    • Organizer
      第34回 日本臨床薬理学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] ALDH2遺伝子多型がニトログリセリンの単回および長期投与効果に及ぼす影響2013

    • Author(s)
      吉原 達也、白石 富美恵、有馬 久富、高橋 富美、池松 秀之、笹栗 俊之
    • Organizer
      第23回日本循環薬理学会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] MRP4遺伝子多型がトリクロルメチアジド単回投与後の血清尿酸値および尿酸クリアランスに及ぼす影響:パイロットスタディ2013

    • Author(s)
      吉原達也、早水憲吾, 永野晃弘, 有岡将基, 北村悠, 高橋富美, 池松秀之, 有馬久富, 笹栗俊之
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Impact of antihypertensive Dedication adherence on blood pressure control in hypertension : the COMFORT study2012

    • Author(s)
      Matsuiura K, Anna H, Toninaga M, Ohtsubo T, Sasaguri T, Fujii K Fukuhara M, Dezono K, Norinaga Y, Ohta Y Otonari T, Kawasaki J, Kato I. Tsuchihashi T for the COMFORT investigators
    • Organizer
      24 th Scientific Meeting 01 tne International Society of Hyoertension
    • Place of Presentation
      シドニー
    • Related Report
      2012 Annual Research Report
  • [Presentation] Does a combination pill of antihypertensive drugs improve medication adherence in Japanese? : the COMFORT study2012

    • Author(s)
      Matsumura K, Arima H, Tominaga M, Ohtsubo T, Sasaguri T, Fujii K, Fukuhara M, Uezono K, Morinaga Y, Ohta Y Otonari T, Kawasaki J, Kato I, Tsuchihashi T for the COMFORT investigators
    • Organizer
      24th Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      シドニー
    • Related Report
      2012 Annual Research Report
  • [Presentation] MRP4遺伝子多型がトリクロルメチアジド単回投与後の血清尿酸値および尿酸クリアランスに及ぼす影響 : パイロットスタディ2012

    • Author(s)
      吉原達也, 早水憲吾, 永野晃弘, 有岡将基, 北村悠, 高橋富美, 池松秀之, 有馬久富, 笹栗俊之
    • Organizer
      第33回日本臨床薬理学会学術総会
    • Place of Presentation
      宜野湾
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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