• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Genetic analysis of VPS13C in Parkinson's disease

Research Project

Project/Area Number 18K07536
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionJuntendo University

Principal Investigator

Yoshino Hiroyo  順天堂大学, 医学(系)研究科(研究院), 助教 (80338417)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsVPS13C / VPS13遺伝子 / パーキンソン病 / レアバリアント / 発症危険因子 / 疾患感受性遺伝子 / VPS13A/B/D / iPS細胞由来神経細胞 / ミトコンドリア機能 / risk variant / 感受性遺伝子 / VPS13C遺伝子
Outline of Final Research Achievements

VPS13 has four paralog genes namely VPS13A/B/C/D. VPS13 genes relate to several types of neurodegenerative disorders, so we focused on the importance of VPS13 genes in neurodegeneration. To evaluate the significance of VPS13 genes as a risk factor in Parkinson’s disease (PD), we assembled a genetic analysis for VPS13 genes in Japanese PD or PD-related disorders patients and controls. Rare variants were defined by minor allele frequency less than 0.5% in the public gene database. There were significant differences in the frequency of rare non-synonymous variant carriers between PD patients and controls in VPS13B, C, D, suggesting that the VPS13 gene may be a disease susceptibility gene for PD.
To evaluate the pathogenesis of rare variants, we established iPS cells from two patients with two-allelic variants of VPS13C and perform a functional study in dopaminergic neurons generated from iPS cells.

Academic Significance and Societal Importance of the Research Achievements

高齢化社会においてパーキンソン病(PD)は重要な疾患であるが、未だ原因は不明であり、根本的治療の確立には発症機序の解明は急務である。VPS13蛋白の機能は十分に解明されていないが、ミトコンドリア機能やタンパク質分解系への関与が示されており、種々の神経変性疾患の原因遺伝子であるVPS13遺伝子は、神経細胞死の機序解明において重要な遺伝子である。
本研究にて、VPS13CのみならずVPS13遺伝子がPDの疾患感受性遺伝子としての可能性が示された。これは加齢や環境要因ともに発症リスクを高める遺伝的要因の一つであり、PDの大部分を占める孤発性PDの発症機序解明の手掛かりが得られた。

Report

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

    (7 results)

All 2020 2019 2018

All Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Genetic analysis of VPS13A/B/D: paralogous genes of VPS13C in Parkinson's disease2020

    • Author(s)
      吉野浩代
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Genetic and iPSC analysis of the patients with the variants of vacuolar protein sorting 13C gene2020

    • Author(s)
      林田有紗
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Genetic analysis of VPS13A/B/D: paralogous genes of VPS13C in Parkinson’s disease2020

    • Author(s)
      吉野浩代
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Genotype-phenotype analysis of VPS13C variants with familial Parkinson’s disease in Japan.2019

    • Author(s)
      林田有紗
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Genotype-phenotype analysis of VPS13C variants with familial Parkinson’s disease in Japan.2019

    • Author(s)
      林田有紗
    • Organizer
      第13回パーキンソン病・運動障害疾患コングレス
    • Related Report
      2019 Research-status Report
  • [Presentation] Genotype-phenotype analysis of VPS13C variants with Parkinson’s disease in Japan2019

    • Author(s)
      林田有紗
    • Organizer
      日本人類遺伝学会第64回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Mutation analysis of VPS13C in Japanese patients with Parkinson's disease2018

    • Author(s)
      Arisa Hayashida, Yuanzhe Li, Hiroyo Yoshino, Aya Ikeda, Manabu Funayama, Kenya Nishioka, Nobutaka Hattori
    • Organizer
      13th International Meeting on Genetic Epidemiology of Parkinson's Disease
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi