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Practical application to preventive medicine by molecular epidemiological analyses on gout using international consortium framework from Japan

Research Project

Project/Area Number 17H04128
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Epidemiology and preventive medicine
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, 准教授 (00528292)

Co-Investigator(Kenkyū-buntansha) 山本 健  久留米大学, 医学部, 教授 (60274528)
中村 好宏  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, 進学課程, 准教授 (60415255)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords痛風 / 高尿酸血症 / 尿酸トランスポーター / 遺伝子 / 国際コンソーシアム / 予防医学 / 個別化医療 / 尿酸輸送体
Outline of Final Research Achievements

Gout/hyperuricemia is one of lifestyle diseases and is also a risk of hypertension, kidney disease, and stroke. Recent genetic studies implied that genetic factors rather than environmental factors have strong effect as its cause. We have developed Asian international consortium named “AsiaGout” and conducted several researches for the practical application to preventive medicine by molecular pathophysiological analyses on gout with other international consortiums. As results, we have identified many disease-associated loci and revealed that Japanese has evolved to have greater genetic effect on the onset of gout. The present research will be helpful to develop genome-personalized preventive method from Japan, as it leads multifactorial disorders including lifestyle diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究では世界最大規模の患者集団の解析を通して、痛風に関連する数多くの遺伝子座と変異の性質が調べられた。さらにアジア国際コンソーシアム”AsiaGout”に加え、より大きな国際コンソーシアムAPGC (Asia Pacific Gout Consortium)も設立され、令和元年7月に研究代表者が大会長として東京で年会を主催した。この国際共同研究の成果として、新規痛風遺伝子座の同定に加え、痛風発症について日本人が遺伝的に影響を受けやすく適応進化した遺伝子座も見出している。このように、本研究はゲノム個別化医療に寄与する、痛風・尿酸関連疾患の分子疫学を日本がリードして進展させる学術的成果を挙げた。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (29 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 4 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) Funded Workshop (1 results)

  • [Int'l Joint Research] チンタオ大学/高雄大学(中国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] オタゴ大学(ニュージーランド)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] プラハ大学(チェコ)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients.2020

    • Author(s)
      Nakayama A, Takada T, et al.
    • Journal Title

      Ann Rheum Dis.

      Volume: 79 Issue: 5 Pages: 657665-657665

    • DOI

      10.1136/annrheumdis-2019-216644

    • NAID

      120007042436

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dysfunctional missense variant of OAT10/SLC22A13 decreases gout risk and serum uric acid levels.2020

    • Author(s)
      Higashino T, Morimoto K, Nakaoka H, Toyoda Y, Kawamura Y, Shimizu S, Nakamura T, Hosomichi K, Nakayama A, Ooyama K, Ooyama H, Shimizu T, Ueno M, Ito T, Tamura T, Naito M, Nakashima H, Kawaguchi M, Takao M, Kawai Y, Osada N, Ichida K, Yamamoto K, Suzuki H, Shinomiya N, Inoue I, Takada T, Matsuo H.
    • Journal Title

      Ann Rheum Dis.

      Volume: 79(1) Issue: 1 Pages: 164-166

    • DOI

      10.1136/annrheumdis-2019-216044

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A common variant of LDL receptor related protein 2 (LRP2) gene is associated with gout susceptibility: a meta-analysis in a Japanese population.2020

    • Author(s)
      Akashi A, Nakayama A, Kamatani Y, Higashino T, Shimizu S, Kawamura Y, Imoto M, Naito M, Hishida A, Kawaguchi M, Takao M, Matsuo M, Takada T, Ichida K, Ooyama H, Shinomiya N, Matsuo H.
    • Journal Title

      Hum Cell.

      Volume: 33 Issue: 2 Pages: 303307-303307

    • DOI

      10.1007/s13577-019-00318-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals2019

    • Author(s)
      Nakatochi M, Kanai M, Nakayama A, Hishida A, Kawamura Y, Ichihara S, Akiyama M, Ikezaki H, Furusyo N, Shimizu S, Yamamoto K, et al.
    • Journal Title

      Commun Biol.

      Volume: 2 Issue: 1 Pages: 115-115

    • DOI

      10.1038/s42003-019-0339-0

    • NAID

      120006937615

    • URL

      https://pure.teikyo.jp/en/publications/d2b1a87f-6b8d-4bb5-a753-843e5cd6647d

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout2019

    • Author(s)
      Kawamura Y, Nakaoka H, Nakayama A, et al.
    • Journal Title

      Ann Rheum Dis

      Volume: 78 Issue: 10 Pages: 1430-1437

    • DOI

      10.1136/annrheumdis-2019-215521

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Common variant of BCAS3 is associated with gout risk in Japanese population: the first replication study after gout GWAS in Han Chinese.2018

    • Author(s)
      Sakiyama M, Matsuo H, Nakaoka H, Kawamura Y, Kawaguchi M, Higashino T, Nakayama A, Akashi A, Ueyama J, Kondo T, Wakai K, Sakurai Y, Yamamoto K, Ooyama H, Shinomiya N.
    • Journal Title

      BMC Med Genet.

      Volume: 19 Issue: 1 Pages: 96-96

    • DOI

      10.1186/s12881-018-0583-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A common variant of MAF/c-MAF, transcriptional factor gene in the kidney, is associated with gout susceptibility.2018

    • Author(s)
      Higashino T, Matsuo H, Okada Y, Nakashima H, Shimizu S, Sakiyama M, Tadokoro S, Nakayama A, Kawaguchi M, Komatsu M, Hishida A, Nakatochi M, Ooyama H, Imaki J, Shinomiya N.
    • Journal Title

      Human Cell

      Volume: 31 Issue: 1 Pages: 10-13

    • DOI

      10.1007/s13577-017-0186-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Independent effects of ADH1B and ALDH2 common dysfunctional variants on gout risk.2017

    • Author(s)
      Sakiyama M, Matsuo H, Akashi A, Shimizu S, Higashino T, Kawaguchi M, Nakayama A, Naito M, Kawai S, Nakashima H, Sakurai Y, Ichida K, Shimizu T, Ooyama H, Shinomiya N.
    • Journal Title

      Scientific Report

      Volume: 7 Issue: 1 Pages: 2500-2500

    • DOI

      10.1038/s41598-017-02528-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes2017

    • Author(s)
      Nakayama A, Nakaoka H, Yamamoto K, Sakiyama M, Shaukat A, Toyoda Y, Okada Y, Ohkawa Y,他39名
    • Journal Title

      Ann Rheum Dis.

      Volume: 76 Issue: 5 Pages: 869

    • DOI

      10.1136/annrheumdis-2016-209632

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Multiple common and rare variants of ABCG2 cause gout2017

    • Author(s)
      Higashino Toshihide、Takada Tappei、Nakaoka Hirofumi、Toyoda Yu、Stiburkova Blanka、Miyata Hiroshi、Ikebuchi Yuki、Nakashima Hiroshi、Shimizu Seiko、Kawaguchi Makoto、Sakiyama Masayuki、Nakayama Akiyoshi、Akashi Airi、Tanahashi Yuki、Kawamura Yusuke、Nakamura Takahiro、Wakai Kenji、Hosomichi Kazuyoshi 他
    • Journal Title

      RMD Open

      Volume: 3 Issue: 2 Pages: e000464-e000464

    • DOI

      10.1136/rmdopen-2017-000464

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] URAT2/OAT10遺伝子の機能低下型ミスセンスSNPは血清尿酸値と痛風のリスクを共に低下させる.2020

    • Author(s)
      河村優輔, 東野俊英, 清水聖子 他.
    • Organizer
      第53回日本痛風・核酸代謝学会総会.
    • Related Report
      2019 Annual Research Report
  • [Presentation] 多様なリガンドのエンドサイトーシスに関わる分子LRP2の一塩基多型rs2544390は痛風発症と関連する:日本人男性における痛風とrs2544390のメタ解析.2020

    • Author(s)
      赤司藍理、中山昌喜、東野俊英 他.
    • Organizer
      第53回日本痛風・核酸代謝学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ゲノムワイド関連解析による無症候性高尿酸血症患者からの痛風発症に関連する新規遺伝子座の同定.2020

    • Author(s)
      松尾洋孝、河村優輔、中岡博史 他.
    • Organizer
      第30回日本疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 日本人における尿酸値のGWASメタ解析: 尿酸値に関わるアレルで制御される遺伝子はtransport関連遺伝子に集約.2019

    • Author(s)
      青柳有香, 中杤昌弘, 金井仁弘 他.
    • Organizer
      第12回トランスポーター研究会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Genome-wide meta-analysis revealed multiple novel loci associated with serum uric acid levels in Japanese.2019

    • Author(s)
      Matsuo H, Nakatochi M, Kanai M et al.
    • Organizer
      European Congress of Rheumatology.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multiple novel loci are associated with serum uric acid levels in Japanese population: a genome-wide meta-analysis.2019

    • Author(s)
      Nakayama A, Nakatochi M, Kanai M et al.
    • Organizer
      18th International Purine and Pyrimidine Symposium.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 日本人121,745人を対象としたゲノムワイドメタ解析により血清尿酸値と関連する8つの新規遺伝子座を同定した.2019

    • Author(s)
      中杤昌弘, 松尾洋孝, 中山昌喜, 他.
    • Organizer
      第52回日本痛風核酸代謝学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 日本人における尿酸のGWASメタ解析による8個の新規遺伝子座の同定.2019

    • Author(s)
      中嶌真由子, 中杤昌弘, 金井仁弘 他.
    • Organizer
      第64回防衛衛生学会.
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高尿酸血症を痛風発症へと増悪させる遺伝要因:ゲノムワイド関連解析から見出された新規遺伝子座.2019

    • Author(s)
      河村優輔, 中岡博史, 中山昌喜 他.
    • Organizer
      第64回日本人類遺伝学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 無症候性高尿酸血症患者が痛風を発症する遺伝的要因:ゲノムワイド関連解析により同定した新規遺伝子座.2019

    • Author(s)
      河村優輔, 松尾洋孝, 中岡博史 他.
    • Organizer
      第37回日本ヒト細胞学会学術集会.
    • Related Report
      2019 Annual Research Report
  • [Presentation] A genome-wide association study identified novel loci associated with the aggravation from asymptomatic hyperuricemia to gout.2019

    • Author(s)
      Kawamura Y, Nakaoka H, Nakayama A et al.
    • Organizer
      Asia-Pacific Gout Consortium 2nd Annual Meeting.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A genome-wide association study identified novel loci associated with the progression from asymptomatic hyperuricemia to gout.2019

    • Author(s)
      Kawamura Y, Nakaoka H, Nakayama A et al.
    • Organizer
      European Congress of Rheumatology.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 無症候性高尿酸血症群と痛風症例群のゲノムワイド関連解析により痛風発症に関連する新規遺伝子座を同定した.2019

    • Author(s)
      河村優輔, 松尾洋孝, 中山昌喜 他.
    • Organizer
      第52回日本痛風核酸代謝学会
    • Related Report
      2019 Annual Research Report
  • [Remarks] 防衛医科大学校分子生体制御学講座ホームページ

    • URL

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

    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 12017

    • Inventor(s)
      2017
    • Industrial Property Rights Holder
      2017
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Funded Workshop] Asia-Pacific Gout Consortium 3rd Annual Meeting (APGC2019)2019

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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