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Investigations for novel moleculs associated with Lp(a)

Research Project

Project/Area Number 19K08575
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionKanazawa University

Principal Investigator

Tada Hayato  金沢大学, 附属病院, 助教 (90623653)

Co-Investigator(Kenkyū-buntansha) 岡田 寛史  金沢大学, 附属病院, 特任助教 (10735161)
野村 章洋  金沢大学, 附属病院, 特任准教授 (30707542)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsリポ蛋白(a) / 網羅的遺伝子解析 / 動脈硬化 / リポタンパク / リポ蛋白
Outline of Research at the Start

既に遺伝子を含めてデータ集積されているリポ蛋白(a)が著明な高値(100 mg/dl以上)を呈する家系および著明な低値(1 mg/dl以下)を呈する家系を対象に全エクソームシークエンス解析を行う。得られた遺伝子変異をその頻度及びin silico病原性予測ツールを用いて絞り込みを行い、最終的に、それぞれ想定される遺伝形式に沿い、遺伝型・表現型のマッチングにより新規原因分子の同定を試みる。新規分子遺伝子変異を有する発端者及び変異を有さない血縁者に対して安定同位体を用いた代謝実験及び疾患特異的iPS細胞を用いた代謝実験により同定した新規分子のリポ蛋白(a)代謝への寄与・メカニズムを明らかとする。

Outline of Final Research Achievements

We identified genetic variants associated with Lp(a) that are common with other ethnicities as well as specific to Japanese. We aldo found that Lp(a) and CRP are associated with worse clinical outcomes aomng patients with familial hypercholesterolemia.

Academic Significance and Societal Importance of the Research Achievements

リポ蛋白(a)と呼ばれるLDLとは独立した動脈硬化危険因子の日本人特有の遺伝的背景を一部明らかとしたほか、日本人においてもリポ蛋白(a)が実際の動脈硬化性疾患と強く関連することを示した。これらの知見は一部新規のものも含まれ、今後の日本人に対する動脈硬化性疾患予防医学への寄与が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report

Research Products

(4 results)

All 2022 2021 2020

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Severe calcification of the Achilles' tendon.2021

    • Author(s)
      Kawashiri MA, Okada H, Tada H.
    • Journal Title

      Eur Heart J

      Volume: 42 Pages: 2217-2217

    • DOI

      10.1093/eurheartj/ehab017

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case with familial hypercholesterolemia complicated with severe systemic atherosclerosis intensively treated for more than 30 years2020

    • Author(s)
      Nishikawa T, Tada H, Nakagawa-Kamiya T, Niwa S, Yoshida S, Mori M, Sakata K, Nohara A, Higashikata T, Kato H, Ino K, Takemura H, Takamura M, Kawashiri MA
    • Journal Title

      J Cardiol Cases

      Volume: 8 Pages: 1809-1813

    • DOI

      10.1016/j.jccase.2020.06.012

    • Related Report
      2020 Research-status Report
  • [Journal Article] Lipoprotein(a) and the Risk of Chronic Kidney Disease in Hospitalized Japanese Patients2020

    • Author(s)
      Tada H, Yamagami K, Nishikawa T, Teramoto R, Sakata K, Takamura M, Kawashiri MA.
    • Journal Title

      Internal Medicine

      Volume: -

    • NAID

      130007873287

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Investigation of Genetic Backgrounds Contributing to Lp(a) levels among Japanese Population2022

    • Author(s)
      Yamagami K, Tada H, Kojima N, Nomura A, Usui S, Sakata K, Kawashiri MA, Takamura M
    • Organizer
      第86回 日本循環器学会学術集会
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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