2022 Fiscal Year Final Research Report
Elucidation of the pathophysiology of novel or rare inherited arrhythmia syndromes by using next generation sequencing and patch-clamp techniques
| Project/Area Number |
20K08487
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Gunma University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
倉林 正彦 群馬大学, その他部局等, 名誉教授 (00215047)
金古 善明 群馬大学, 大学院医学系研究科, 准教授 (60302478)
西山 正彦 群馬大学, その他部局等, 名誉教授 (20198526)
川端 麗香 群馬大学, 未来先端研究機構, 講師 (90721928)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 遺伝性不整脈症候群 / 次世代シークエンス / イオンチャネル / 電気生理学 / パッチクランプ法 |
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| Outline of Final Research Achievements |
We sought to elucidate the pathophysiology of inherited arrhythmia syndromes exhibiting novel or rare phenotypes by using next generation sequencing and patch-clamp techniques.
As a result, 1. We identified an SCN5A V1667I mutation in a family of long QT syndrome (LQTS) with epinephrine-induced QT prolongation, and revealed its underlying mechanism. 2. We identified an SCN5A W374G mutation in siblings of Brugada syndrome with severe clinical phenotypes, and revealed that reduced sodium currents by the mutation were partially restored by incubation with mexiletine. 3. We identified a novel CACNA1C R511Q mutation, located in domainⅠ-Ⅱ linker, in an LQTS family (without other cardiac and extra cardiac phenotypes), and revealed that a delay of voltage-dependent inactivation rate causes LQTS alone.
These results provided novel insights into the structure-function relationship of ion channels and genotype-phenotype relationship, and raised a possibility of mutation specific therapies.
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| Free Research Field |
循環器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
稀有な表現型を呈する遺伝性不整脈症候群の病態を解明し得た。また、イオンチャネル関連遺伝子の構造機能連関、及び、遺伝子型-表現型についても新たな知見をもたらした。さらに、遺伝子変異特異的治療法や新規治療法につながる基礎的基盤を構築し得た。今後、我々の研究成果が基礎研究及び臨床研究に波及し、実際に臨床に還元されることが期待される。
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