| Project/Area Number |
26870438
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
Medical genome science
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| Research Institution | Nagasaki University |
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Principal Investigator |
INAMINE Tatsuo 長崎大学, 医歯薬学総合研究科(薬学系), 助教 (00549628)
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| Research Collaborator |
IGAWA Chizuru
UNOIKE Miki
GOTO Natsumi
MAKIMOTO Ayaka
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 遺伝子多型 / 胆汁酸 / 薬物治療 / 胆汁うっ滞性肝疾患 / ウルソデオキシコール酸 / 原発性胆汁性胆管炎 / 薬剤反応性 / CYP7A1 / 原発性胆汁性肝硬変 |
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| Outline of Final Research Achievements |
The original research goal was to reveal mechanisms underlying individual difference of reactivity to ursodeoxycholic acid (UDCA) or bezafibrate treatment in Japanese patients with primary biliary cholangitis (PBC). In the study, genetic polymorphisms of CYP7A1, which is the rate-limiting enzyme in the classical bile acid synthetic pathway, as well as of PGC-1α, which is a transcriptional inducer of CYP7A1, were not associated with UDCA response of PBC patients. Reporter gene assay demonstrated that bezafibrate does not affect neither activity of CYP7A1 promoter nor function of the promoter SNP of CYP7A1. On the other hand, rs8192678 that is a missense variant of PGC-1α was shown to be involved in hepatic CYP7A1 activity in a healthy Japanese.
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