The risk stratification of drug-induced long QT syndrome upon the underlying genetics
| Project/Area Number |
17K09494
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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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| Research Field |
Cardiovascular medicine
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| Research Institution | Hiroshima University (2019)
Shiga University of Medical Science (2017-2018) |
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Principal Investigator |
Itoh Hideki 広島大学, 病院(医), 教授 (30402738)
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| Co-Investigator(Kenkyū-buntansha) |
大野 聖子 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (20610025)
松浦 博 滋賀医科大学, 医学部, 教授 (60238962)
堀江 稔 滋賀医科大学, アジア疫学研究センター, 特任教授 (90183938)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 個別化医療 / 突然死 / 薬剤 / 遺伝子 / QT延長 / QT延長症候群 / 薬剤性 / 多型 / 後天性 |
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| Outline of Final Research Achievements |
This study revealed that patients with drug-induced QT prolongation and/or fatal arrhythmias failed to carry a mutation in minor candidate genes corresponding to congenital long QT syndrome. The frequency of polymorphisms in CYP genes were similar between drug-induced long QT syndrome and normal control cohorts. We are able to establish the risk stratification based on the underlying genetics including LQT1-LQT3, QT interval at baseline, gender and age upon this study.
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| Academic Significance and Societal Importance of the Research Achievements |
薬剤性QT延長症候群の遺伝的背景に、5つの責任遺伝子(KCNQ1:LQT1, KCNH2:LTQ2, SCN5A:LQT3, KCNE1:LQT5, KCNE2:LQT6)以外のminor geneはcontributionが小さいことが明らかになった。薬剤性QT延長症候群の予防・管理においては、保険診療として実施しうるLQT1-3の3つのサブタイプの有無とQT間隔、性別・年齢等を加味した、risk stratificationの構築が実用的であることが示された。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation.2018
Author(s)
Ueshima S, Hira D, Kimura Y, Fujii R, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Ohno S, Horie M, Terada T, Katsura T.
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Journal Title
Br. J. Clin. Pharmacol.
Volume: -
Issue: 6
Pages: 1301-1312
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impact of ABCB1, ABCG2, and CYP3A5 polymorphisms on plasma trough concentrations of apixaban in Japanese patients with atrial fibrillation2017
Author(s)
Satoshi Ueshima, Daiki Hira, Ryo Fujii, Yuuma Kimura, Chiho Tomitsuka, Takuya Yamane, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Minoru Horie, Tomohiro Terada, Toshiya Katsura
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Journal Title
Pharmacogenetics and Genomics
Volume: 27
Issue: 9
Pages: 329-336
DOI
Related Report
Peer Reviewed
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[Presentation] Genetic background in patients with idiopathic ventricular fibrillation: known gene screening from whole exome analysis data2018
Author(s)
Aiba T, Cha PC, Takahashi A, Ohno S, Kamakura T, Ishikawa T, Ishibashi-Ueda H, Shiba-Harada M, Minamino N, Hayashi K, Yagihara N, Nakano Y, Itoh H, Miyamoto Y, Tanaka T, Makita N, Horie M, Shimizu W, Kusano K, Yasuda S.
Organizer
The 83rd Annual Scientific Meeting of the Japanese Circulation Society
Related Report
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