Quality control of protein in cardiomyochyte by atrial fibrillation associated gene, NEURL1
Project/Area Number |
17K07251
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Medical genome science
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Ebana Yusuke 東京医科歯科大学, 統合研究機構, 講師 (60517043)
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Project Period (FY) |
2017-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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Keywords | 心房細動 / ゲノムワイド関連研究 / mTOR / mTOR / NEURL / タンパク質品質管理 / 機能解析 / 心筋細胞 |
Outline of Final Research Achievements |
Pathway analysis was performed from all SNV data used in genome-wide association studies to identify the CTCF and mTOR pathways. In order to confirm the involvement of the CTCF pathway and the mTOR pathway, microarray analysis was performed using atrial muscle tissue specimens collected in Department of Cardiovascular Surgery. Examination of the involvement of the two pathways in patients with atrial fibrillation and non-atrial fibrillation showed that the mTOR pathway was suppressed in the atrial muscles collected from patients with atrial fibrillation. By participating in multi-institutional joint research on atrial fibrillation, we have newly identified a genetic predisposition related to atrial fibrillation.
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Academic Significance and Societal Importance of the Research Achievements |
ゲノムワイド関連研究から同定された遺伝マーカーから、心房細動に関連する生物学的経路を同定した。トランスクリプトーム解析から心房細動においてはmTOR経路が抑制されている可能性があり、心筋細胞におけるエネルギー代謝障害や機能タンパク質の品質管理に障害が生じていることが示唆された。心房筋の細胞障害の原因に光を当てることで、心房細動の薬物的な治療への可能性を開いたという意義がある。 また国際共同研究を含む、様々な共同研究を通して新たに心房細動に関わる遺伝子や遺伝子座が同定され、結果として遺伝的リスク評価法が提案され、臨床的な意義があると考えられる。
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Report
(6 results)
Research Products
(12 results)
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[Journal Article] Mutant KCNJ3 and KCNJ5 potassium channels as novel molecular targets in bradyarrhythmias and atrial fibrillation.2019
Author(s)
Yamada N, Asano Y, Fujita M, Yamazaki S, Inanobe A, Matsuura N, Kobayashi H, Ohno S, Ebana Y, Tsukamoto O, Ishino S, Takuwa A, Kioka H, Yamashita T, Hashimoto N, Zankov DP, Shimizu A, Asakura M, Asanuma H, Kato H, Nishida Y, Miyashita Y, Shinomiya H, Naiki N, Hayashi K, Makiyama T, Ogita H, et al.
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Journal Title
Circulation
Volume: In press
Issue: 18
Pages: 2157-2169
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Association of the Clinical and Genetic Factors With Superior Vena Cava Arrhythmogenicity in Atrial Fibrillation2018
Author(s)
Ebana Y, Nitta J, Takahashi Y, Miyazaki S, Suzuki M, Liu L, Hirao K, Kanda E, Isobe M, Furukawa T
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Journal Title
Circulation Journal
Volume: 82
Issue: 1
Pages: 71-77
DOI
NAID
ISSN
1346-9843, 1347-4820
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of six novel genetic loci associated with atrial fibrillation in Japanese population.2017
Author(s)
Low SK, Takahashi A, Ebana Y, Ozaki K, Christophersen IE, Ellinor PT, AFGen Consortium, Ogishima S, Yamamoto M, Satoh M, Sasaki M, Yamaji T, Iwasaki M, Tsugane S, Tanaka K, Naito M, Wakai K, Tanaka H, Furukawa T, Kubo M, Ito K, Kamatani Y, Tanaka T.
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Journal Title
Nature Genetics
Volume: -
Issue: 6
Pages: 953-958
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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