2023 Fiscal Year Final Research Report
Single-molecule analysis of somatic mitochondrial DNA mutations in mood disorder
| Project/Area Number |
21K15722
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | ミトコンドリアDNA / 一分子解析 / 双極性障害 / ヘテロプラスミー / 死後脳 / m.3243A>G / ミトコンドリア病 / MELAS |
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| Outline of Final Research Achievements |
I performed postmortem brain mtDNA analysis on 54 patients with bipolar disorder and 54 controls. Cases and controls were compared for heteroplasmy mutations with an allele fraction of 1% or more and mitochondrial DNA mutation rates per base. Cases were more likely to have heteroplasmy mutations with an allele ratio of 1% or more than controls, with a particularly notable difference in rRNA rare heteroplasmy, with 6 cases and 0 controls. The m.3243A>G variant, which is the causative variant of mitochondrial disease MELAS, was detected in two patients with bipolar disorder but none in the controls. Meanwhile, there was no difference in mitochondrial DNA single molecule mutation rates between cases and controls.
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| Free Research Field |
精神医学
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| Academic Significance and Societal Importance of the Research Achievements |
m.3243A>Gバリアントは、Nishioka et al. Molecular Psychiatry 2023において双極性障害2名からの検出を報告し、死後脳試料における新たな解析でも、支持的な結果を得た。双極性障害の一部が、ミトコンドリアDNAの稀なヘテロプラスミー変異で説明できる可能性を示唆する。双極性障害におけるヘテロプラスミー変異の濃縮は、ミトコンドリアDNA全体の変異率上昇でなく、効果の高いバリアントがドリフトし、確率的に割合が多くなった結果と考えられ、双極性障害の病態理解に貢献した。ミトコンドリアDNAバリアントによる双極性障害の層別化を示し、今後の薬剤開発の基礎を示した。
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