Identification of genetic and environmental risk factors for moyamoya disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K19963
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Kyoto University
• Principal Investigator: MINEHARU Yohei 京都大学, 医学研究科, 助教 (50716602)
• Research Collaborator: MATSUDA yoshiko ; MORIMOTO takaaki ; FUNAKI takashi ; KATAOKA hiroharu ; HARADA H kouji ; HIGASA koichiro ; TABARA yasuharu ; MATSUDA fumihiko ; KOIZUMI akio ; MIYAMOTO susumu
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: moyamoya disease / genetics / environmental risk / cerebrovascular disease / atherosclerosis / coronary artery disease

Outline of Final Research Achievements

We aimed to determine the significance of the R4810K mutation in RNF213 gene in clinical settings. We also aimed to identify genetic factors other than RNF213 and environmental risk factors for moyamoya disease. First, we found that the R4810K mutation was associated not only with moyamoya disease but moyamoya syndrome or coronary artery disease. For family members of patients with moyamoya disease, carrier of the R4810K mutation had high risk of cerebrovascular disease as one of four carriers had stenoocclusive lesions. Whole genome sequencing of patients without the R4810K mutation identified several candidate genes for moyamoya disease. As for environmental risk factors, we found the non-genetic factor which was associated with disease progression of unilateral moyamoya disease.

Free Research Field

neurosurgery

Academic Significance and Societal Importance of the Research Achievements

もやもや病は日本人を含めた東アジアに多い脳血管の病気です。もやもや病の原因遺伝子として我々が特定したRNF213遺伝子のR4810K変異は、もやもや病以外の脳血管障害のリスクにもなっていることが分かってきました。本研究により、R4810K変異が頭蓋内血管のみならず、冠動脈など頭蓋外の血管狭窄にも関わっていることを明らかにしました。もやもや病発症には、RNF213遺伝子変異以外の要因も大切であることが分かっており、本研究を通じて、別の候補遺伝子を特定することに成功しました。また、環境要因の一つを明らかにすることもでき、今後病気の全容解明に繋げられると期待されます。