| Project/Area Number |
16K09070
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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 |
Epidemiology and preventive medicine
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| Research Institution | Kyorin University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平野 照之 杏林大学, 医学部, 教授 (50346996)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 直接阻害型経口抗凝固薬 / 脳梗塞 / 脳塞栓症 / ファーマコゲノミクス / 一塩基多型 / CES1 / ABCB1 / DOAC / 経口抗凝固薬 / 脳塞栓 / 新規経口抗凝固薬 |
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| Outline of Final Research Achievements |
This prospective study was aimed to identify biomarkers for bleeding risk of direct oral anticoagulants (DOAC) in cerebral stroke patients. We investigated the allele frequencies and the genotypes of CES1: rs2244613 and ABCB1: rs4148738 polymorphisms in 22 Japanese patients with cerebral stroke. These polymorphisms were reported to be associated with the dabigatran concentrations and the risk of bleeding in dabigatran-treated Caucasian patients. The minor allele (C allele) of CES1: rs2244613 polymorphism was associated with lower trough concentrations and a lower risk of bleeding (Circulation, 2013). In our Japanese patients, the C allele frequency of CES1: rs2244613 polymorphism was 52%, which was higher than in the Caucasian participants of RE-LY Trial (18%). Bleeding events have not occurred in our patients during this study. Further studies are needed to clarify the association between the polymorphisms and the bleeding risk of DOAC in Japanese patients with cerebral stroke.
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| Academic Significance and Societal Importance of the Research Achievements |
脳塞栓症の二次予防を目的とした抗凝固療法において、ワルファリンに代わり、DOACが使われるようになった。DOACは血液凝固機能のモニタリングは不要とされるが、適切な薬物療法を行うために、出血性副作用を回避する指標が求められている。本研究は、欧米の先行研究でDOACとの関連が明らかとなった遺伝子多型について、日本人で検証した。年齢と腎機能の観点からDOACを選択したところ、現時点までに脳梗塞再発および出血性副作用はみられていない。今後も経過を追って、出血性副作用と遺伝子型との関連を検討していく。出血性副作用を予測するバイオマーカーの同定は、個人の薬物代謝能力に応じた個別化治療への礎となる。
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