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International collaborative study on the genetic factors that regulate serum urate levels in humans: clinico-genetic analyses and functional studies focusing on urate transporters

Research Project

Project/Area Number 21KK0173
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 58:Society medicine, nursing, and related fields
Research InstitutionNational Defense Medical College

Principal Investigator

Matsuo Hirotaka  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 分子生体制御学, 教授 (00528292)

Co-Investigator(Kenkyū-buntansha) 関根 舞  東京薬科大学, 薬学部, 助教 (40881496)
豊田 優  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 分子生体制御学, 講師 (80650340)
宮田 大資  東京大学, 医学部附属病院, 助教 (90844415)
Project Period (FY) 2021-10-07 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2023: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2022: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2021: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords尿酸 / 高尿酸血症 / 痛風 / GWAS / 国際共同研究
Outline of Research at the Start

近年、血清尿酸値に寄与する遺伝要因の理解が進んできました。ところが、その全貌は依然として不明なままです。この課題の解決を目指すにあたり、本研究では、日本人と異なる遺伝的背景を有する人々から成るニュージーランドを相手国とする国際共同研究を立案しました。血清尿酸値や尿酸関連疾患リスクに影響する遺伝要因の探索・同定を目的とした研究を実施するとともに、若手研究者を中心とする人材交流を促進することで、国際共同研究基盤のさらなる強化を図ります。

Outline of Final Research Achievements

Recent advances in genomic research have accelerated the understanding of genetic factors that regulate serum urate levels in humans. However, the whole picture of the genetic factors remains to be elucidated. To address this issue, we, Japanese researchers, have organized an international collaborative research. The research period was from October 2021 to March 2024. To achieve the goal of this proposal, we conducted clinico-genetic analyses in combination with functional studies for urate transporters. We believe that our results obtained in this study will improve understanding of the genetic factors regulating uric acid levels in humans. Also, they also have the potential to contribute to the provision and utilization of more useful information in medical treatment and prevention based on individual genomic differences, and further developments are expected in the future.

Academic Significance and Societal Importance of the Research Achievements

血清尿酸値、ひいては痛風に代表される尿酸関連疾患リスクの遺伝要因には、依然として不明な点が多く、その全貌解明に向けた研究の推進には社会的にも大きな関心が払われてきました。本国際共同研究は、この課題を解決するための一助となるべく企画された2年半研究であり、痛風リスクや血清尿酸値の個人差に関連する遺伝要因のさらなる理解に貢献する多くの知見を得ることに成功しました。得られた成果は、痛風の発症メカニズムの解明や創薬へと繋がりうるのみならず、ゲノムの個人差に基づく医療・予防においてより有用な情報の提供・活用に資する可能性を秘めており、今後のさらなる発展が期待されます。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (23 results)

All 2024 2023 2022 Other

All Int'l Joint Research (7 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results) Remarks (1 results)

  • [Int'l Joint Research] Otago University(ニュージーランド)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University of Alabama(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Otago University(ニュージーランド)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] University of Alabama(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Otago University(ニュージーランド)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Shanghai Jiao Tong University/Qingdao University(中国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] National University of Kaohsiung, Taiwan/Kaohsiung Medical University, Taiwan(その他の国・地域)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout2023

    • Author(s)
      Sumpter Nicholas A.、Takei Riku、Cadzow Murray、Topless Ruth K. G.、Phipps‐Green Amanda J.、Murphy Rinki、de Zoysa Janak、Watson Huti、Qasim Muhammad、Lupi Alexa S.、Matsuo Hirotaka、et al., Merriman Tony R.
    • Journal Title

      Arthritis & Rheumatology

      Volume: 75 Issue: 5 Pages: 816-825

    • DOI

      10.1002/art.42393

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dysuricemia.2023

    • Author(s)
      Nakayama A, Kurajoh M, Toyoda Y, Takada T, Ichida K, Matsuo H.
    • Journal Title

      Biomedicines

      Volume: 11 Issue: 12 Pages: 3169-3169

    • DOI

      10.3390/biomedicines11123169

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] OAT10/SLC22A13 Acts as a Renal Urate Re-Absorber : Clinico-Genetic and Functional Analyses With Pharmacological Impacts2022

    • Author(s)
      Yu Toyoda, Yusuke Kawamura, Akiyoshi Nakayama, Keito Morimoto, Seiko Shimizu, Yuki Tanahashi, Takashi Tamura, Takaaki Kondo, Yasufumi Kato, Hirotaka Matsuo, et al.
    • Journal Title

      Frontiers in Pharmacology

      Volume: 13 Pages: 842717-842717

    • DOI

      10.3389/fphar.2022.842717

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Coffee Consumption Reduces Gout Risk Independently of Serum Uric Acid Levels: Mendelian Randomization Analyses Across Ancestry Populations2022

    • Author(s)
      Shirai Yuya、Nakayama Akiyoshi、Kawamura Yusuke、Toyoda Yu、Nakatochi Masahiro、Shimizu Seiko、Shinomiya Nariyoshi、Okada Yukinori、Matsuo Hirotaka、Japan Gout Genomics Consortium (Japan Gout)
    • Journal Title

      ACR Open Rheumatology

      Volume: - Issue: 6 Pages: 534-539

    • DOI

      10.1002/acr2.11425

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A meta-analysis of genome-wide association studies using Japanese and Taiwanese has revealed novel loci associated with gout susceptibility2022

    • Author(s)
      Chang Shun-Jen、Toyoda Yu、Kawamura Yusuke、Nakamura Takahiro、Nakatochi Masahiro、Nakayama Akiyoshi、et al.
    • Journal Title

      Human Cell

      Volume: 35 Issue: 2 Pages: 767-770

    • DOI

      10.1007/s13577-021-00665-2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genome-wide meta-analysis between renal overload type and renal underexcretion type of clinically defined gout in Japanese populations2022

    • Author(s)
      Toyoda Yu、Nakayama Akiyoshi、Nakatochi Masahiro、Kawamura Yusuke、Nakaoka Hirofumi、Yamamoto Ken、Shimizu Seiko、Ooyama Hiroshi、Ooyama Keiko、Shimizu Toru、Nagase Mitsuo、Hidaka Yuji、Ichida Kimiyoshi、Inoue Ituro、Shinomiya Nariyoshi、Matsuo Hirotaka
    • Journal Title

      Molecular Genetics and Metabolism

      Volume: - Issue: 3 Pages: 00126-3

    • DOI

      10.1016/j.ymgme.2022.01.100

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 痛風の主要病因遺伝子の発見とゲノムワイド関連解析による遺伝子の個人差の解明2024

    • Author(s)
      松尾洋孝
    • Organizer
      第57回日本痛風・尿酸核酸学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 臨床診断された痛風患者のみによる病型分類別のゲノムワイド関連解析および遺伝率2024

    • Author(s)
      中山昌喜, 豊田優, 中杤昌弘, 河村優輔, 中岡博史, 市田公美, 高田龍平, 清水聖子, 清水徹, 大山博司, 大山恵子, 長瀬満夫, 日高雄二, 高田雄三, 四ノ宮成祥, 松尾洋孝
    • Organizer
      第57回日本痛風・尿酸核酸学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] コーヒー摂取の習慣は血清尿酸値とは相関せずに痛風リスクを減少させる:日欧の人種集団におけるメンデルランダム化解析より2024

    • Author(s)
      大西まなみ, 白井雄也, 野原悠希, 中山昌喜, 河村優輔, 豊田優, 染谷真澄, 中杤昌弘, 清水聖子, 四ノ宮成祥, 岡田随象, 松尾洋孝
    • Organizer
      第69回防衛衛生学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 臨床診断された痛風患者のみによる病型分類別のゲノムワイド関連解析と遺伝率2024

    • Author(s)
      松尾洋孝, 豊田優, 中杤昌弘, 中山昌喜, 河村優輔, 清水聖子, 中岡博史, 若井建志, 松尾恵太郎
    • Organizer
      第34回日本疫学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Recent Genetic Analyses of Gout and Dysuricemia2023

    • Author(s)
      Matsuo, H., Nakayama A., Takada T., Okada Y., Ichida K
    • Organizer
      G-CAN 9th Annual Research Symposium
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Physiological and pharmacological characterization of OAT10/SLC22A13, a urate re-absorber in the kidney2023

    • Author(s)
      Takada, T., Toyoda Y., Kawamura Y., Nakayama A., Morimoto K., Shimizu S., Shinomiya N., Kobayashi Y., Ichida K., Matsuo H
    • Organizer
      The 20th Symposium on Purine and Pyrimidine Metabolism in Man (PP23)
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Clinico-genetics analyses of gout and urate: Recent progresses from Japan2022

    • Author(s)
      H. Matsuo, Y. Shirai, Y. Kawamura, Y. Toyoda, M. Nakatochi, A. Nakayama, S. Shimizu, T. Takada, K. Ichida, N. Shinomiya, Y. Okada
    • Organizer
      Asia-Pacific Gout Consortium 5th Annual Meeting/12th Oriental gout symposium
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] A Genome-Wide Association Analysis of 2,622,830 Individuals Reveals New Pathogenic Pathways in Gout2022

    • Author(s)
      TR. Merriman, H. Matsuo, R. Takei, M. Leask, R. Topless, Y. Shirai , Z. Li, M. et al
    • Organizer
      ACR Convergence 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mendelian randomization analyses revealed that coffee consumption reduces gout risk independently of serum uric acid levels2022

    • Author(s)
      A. Nakayama, Y. Shirai, Y. Kawamura, Y. Toyoda, M. Nakatochi, S. Shimizu, N. Shinomiya, Y. Okada, H. Matsuo
    • Organizer
      European Crystal Network Workshop 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Remarks] 防衛医科大学校 分子生体制御学講座

    • URL

      http://ndmc-ipb.browse.jp/member.shtml

    • Related Report
      2023 Annual Research Report 2022 Research-status Report 2021 Research-status Report

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Published: 2021-10-22   Modified: 2025-01-30  

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