Elucidation of mplecular mechanism of multiple system atrophy employing a patient registry system

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02739
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Mitsui Jun 東京大学, 医学部附属病院, 特任准教授 (70579862)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 多系統萎縮症 / 関連解析

Outline of Final Research Achievements

Genetic analyses (whole genome analysis, whole exome analysis, and genome-wide SNP typing) were performed in patients with multiple system atrophy and normal healthy controls to search for disease susceptibility genes for multiple system atrophy by association studies. Functional analysis was also performed on tissue samples from patients.
As a result, the association with the COQ2 gene was further established by meta-analysis, and the pathogenesis of multiple system atrophy caused by the COQ2 gene variants was investigated. Furthermore, a genome-wide association study identified a novel disease susceptibility gene.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

多系統萎縮症は，原因不明で，有効な治療法の乏しい神経変性疾患である．疾患関連遺伝子の同定と，機能ならびに病態との関連を理解することは，治療法開発のもっとも重要な手がかりになる．本研究では，COQ2遺伝子と多系統萎縮症との遺伝学的な関連を確立するとともに，COQ2遺伝子と機能並びに病態との関連について，様々な理解を深めた．さらにゲノムワイド関連解析によって，新たな疾患関連遺伝子の候補を同定した．