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原発開放隅角緑内障発症進行メカニズムの解明 -感受性遺伝子多型の表現型への関与-

Research Project

Project/Area Number 18K09400
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionUniversity of Yamanashi

Principal Investigator

間渕 文彦  山梨大学, 大学院総合研究部, 医学研究員 (20322125)

Co-Investigator(Kenkyū-buntansha) 柏木 賢治  山梨大学, 大学院総合研究部, 教授 (30194723)
櫻田 庸一  山梨大学, 大学院総合研究部, 講師 (90456476)
米山 征吾  山梨大学, 大学院総合研究部, 助教 (90751652)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Granted (Fiscal Year 2019)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords原発開放隅角緑内障 / 遺伝子多型 / 眼圧 / genetic risk score / 家族歴 / 診断時年齢 / POAG / IOP / polygenic risk score / 感受性遺伝子多型
Outline of Annual Research Achievements

原発開放隅角緑内障(POAG)感受性遺伝子多型は、眼圧(IOP)上昇に関与するIOP-related遺伝子多型と、眼圧とは別に視神経の脆弱性に関与するnon-IOP-related遺伝子多型の2つに分類される。我々は、眼圧がIOP-related遺伝子多型の相加効果により上昇すること、IOP-related遺伝子多型、non-IOP-related遺伝子多型をどのくらい持つかによって、正常眼圧緑内障、狭義POAG、高眼圧症いずれかの表現型を呈する可能性を報告した。本研究では、POAG発症にはnon-IOP-related遺伝子多型、進行にはIOP-related遺伝子多型が重要な役割を果たしていることを検証する。
今年度は、IOP-related遺伝子多型であるrs945686 (近傍の遺伝子: LMX1B)、rs10505100 (ANGPT1)、rs61394862 (ANKH)、rs7924522 (ETS1)、non-IOP-related遺伝子多型と思われるrs61861119 (MYOF)の遺伝子型をTaqMan genotyping assay法にて同定。POAG感受性遺伝子多型の相加効果を評価するため、複数のIOP-related遺伝子多型のrisk allele数の合計をgenetic risk score (GRS)として各症例毎に算出。同様にnon-IOP-related遺伝子多型についてもGRSを算出した。POAG発症リスクの指標を緑内障家族歴、進行リスクの指標を緑内障診断時年齢としてGRSとの関係について検討したところ、緑内障家族歴(発症)にはnon-IOP-related遺伝子多型(視神経脆弱性)、緑内障診断時年齢(進行)にはIOP-related遺伝子多型(眼圧上昇)が重要な役割を果たしていることを見出したので報告した。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

POAG発症にはnon-IOP-related遺伝子多型、進行にはIOP-related遺伝子多型が重要な役割を果たしていることを見出すことができ、予定通りの進捗状況となっている。

Strategy for Future Research Activity

POAG感受性遺伝子多型解析を進めるとともに、視野検査を含む臨床データの収集を継続して行っていく。IOP-related遺伝子多型、non-IOP-related遺伝子多型に加え、検索したすべてのPOAG感受性遺伝子多型のgenetic risk scoreを算出し、視野障害パターンや進行度、POAG発症リスク評価、眼圧上昇予測、POAG発症年齢予測のための基礎データを構築していく。

Report

(2 results)
  • 2019 Research-status Report
  • 2018 Research-status Report

Research Products

(17 results)

All 2020 2019 2018 Other

All Int'l Joint Research Journal Article Presentation Book

  • [Int'l Joint Research] New York University School of Medicine(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Singapore National Eye Centre/Duke-NUS Medical School/National University of Singapore(シンガポール)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Harvard Medical School/Duke University/Case Western Reserve University(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Flinders University/University of Melbourne/University of Tasmania(オーストラリア)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Ibadan(ナイジェリア)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Ghana(ガーナ)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2018 Research-status Report
  • [Journal Article] Genetic Variants Associated With the Onset and Progression of Primary Open-Angle Glaucoma2020

    • Author(s)
      Mabuchi F, Mabuchi N, Sakurada Y, Yoneyama S, Kashiwagi K, Iijima H, Yamagata Z, Takamoto M, Aihara M, Iwata T, Hashimoto K, Sato K, Shiga Y, Nishiguchi KM, Nakazawa T, Akiyama M, Kawase K, Ozaki M, Araie M, Japan Glaucoma Society Omics Group (JGS-OG)
    • Journal Title

      Am J Ophthalmol

      Volume: 212 Pages: 135-140

    • DOI

      10.1016/j.ajo.2020.03.014

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genetic factors associated with response to as-needed aflibercept therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy2020

    • Author(s)
      Yoneyama S, Sakurada Y, Kikushima W, Sugiyama A, Matsubara M, Fukuda Y, Tanabe N, Parikh R, Mabuchi F, Kashiwagi K, Iijima H
    • Journal Title

      Sci Rep

      Volume: 10 Pages: 7188-7188

    • DOI

      10.1038/s41598-020-64301-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genome-wide association study identifies seven novel susceptibility loei for primary open-angle glaucoma2018

    • Author(s)
      Shiga Y, Akiyama M, Nishiguchi K M, Sato K, Shimozawa N, Takahashi A, Momozawa Y, Hirata M, Matsuda K, Yamaji T, Iwasaki M, Tsugane S, Oze I, Mikami H, Naito M, Wakai K, Yoshikawa M, Miyake M, Yanaka T, et al.
    • Journal Title

      Human Molecular Genetics

      Volume: 27 Issue: 8 Pages: 1486-1496

    • DOI

      10.1093/hmg/ddy053

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Genetic variants associated with progression of visual field defect in primary open-angle glaucoma2019

    • Author(s)
      Mabuchi F, Mabuchi N, Sakurada Y, Yoneyama S, Kashiwagi K, Iijima H, Yamagata Z, Takamoto M, Aihara M, Iwata T, Kawase K, Hashimoto K, Sato K, Shiga Y, Nishiguchi KM, Nakazawa T, Ozaki M, Araie M, for the Japan Glaucoma Society Omics Group (JGS-OG)
    • Organizer
      World Glaucoma Congress (WGC)
    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prediction of glaucomatous visual field progression by genetic variants associated with primary open-angle glaucoma2019

    • Author(s)
      Mabuchi F, Mabuchi N, Sakurada Y, Yoneyama S, Kashiwagi K, Iijima H, Yamagata Z, Takamoto M, Aihara M, Iwata T, Hashimoto K, Sato K, Shiga Y, Nishiguchi KM, Nakazawa T, Akiyama M, Kawase K, Ozaki M, Araie M, for the Japan Glaucoma Society Omics Group (JGS-OG)
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Method for predicting disease onset risk by genetic variants associated with primary open-angle glaucoma2019

    • Author(s)
      Mabuchi F, Mabuchi N, Sakurada Y, Yoneyama S, Kashiwagi K, Yamagata Z, Iijima H, for the Japan Glaucoma Society Omics Group (JGS-OG)
    • Organizer
      American Society of Human Genetics (ASHG)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Association between additive effects of genetic variants associated with primary open-angle glaucoma and family history of glaucoma2018

    • Author(s)
      Mabuchi F, Mabuchi N, Sakurada Y, Yoneyama S, Kashiwagi K, Yamagata Z, Iijima H, for the Japan Glaucoma Society Omics Group (JGS-OG)
    • Organizer
      European Glaucoma Society (EGS)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Association between additive effects of genetic variants associated with primary open-angle glaucoma and age at diagnosis of glaucoma2018

    • Author(s)
      Mabuchi F, Mabuchi N, Sakurada Y, Yoneyama S, Kashiwagi K, Iijima H, Yamagata Z, Takamoto M, Aihara M, Iwata T, Kawase K, Shiga Y, Nishiguchi KM, Nakazawa T, Ozaki M, Araie M, for the Japan Glaucoma Society Omics Group (JGS-OG)
    • Organizer
      American Society of Human Genetics (ASHG)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 多型解析によるPOAG発症進行メカニズム解明とリスク予測 ―スクリーニングチップ臨床応用にむけて―2018

    • Author(s)
      間渕文彦
    • Organizer
      日本緑内障学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] 眼科2018

    • Author(s)
      間渕文彦
    • Total Pages
      7
    • Publisher
      金原出版
    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2021-01-27  

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