Search for new theraputic targets for intracranial artery stenosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: The University of Tokyo
• Principal Investigator: Miyawaki Satoru 東京大学, 医学部附属病院, 講師 (70407914)
• Co-Investigator(Kenkyū-buntansha): 中冨 浩文 東京大学, 医学部附属病院, 准教授 (10420209) ; 齊藤 延人 東京大学, 医学部附属病院, 教授 (60262002)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 脳血管狭窄 / RNF213 / GWAS / PheWAS

Outline of Final Research Achievements

In this study, we aimed to elucidate the pathogenesis of intracranial artery stenosis through various genetic analyses. First, we identified ICAS-associated rare RNF213 variants by targeting the entire RNF213. Second, we searched the whole genome region for variants associated with intracranial artery stenosis and found that the only significant associated variant was RNF213 p.Arg4810Lys. Finally, we searched for genetic factors other than RNF213 p.Arg4810Lys that determine the severity of intracranial artery stenosis and identified a candidate gene. Further functional analysis of this gene will help elucidate the mechanism of intracranial artery stenosis.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

脳血管狭窄に関して、発展的な遺伝子解析研究を行い新たな知見を多く得た。脳血管狭窄に限定した遺伝子解析研究は独自性が高く学術的意義は高いと考えられる。脳血管狭窄の重症度に関連する同定しており、さらなる研究の発展が期待される。脳血管狭窄のは日本はじめとした東アジアに多く発症することが知られており、その病態解明は社会的意義が高いと考える。