Analysis of epigenetic mechanisms on the regulation of drug metabolizing enzymes and its application to personalized drug therapy
| Project/Area Number |
24590451
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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 |
Human pathology
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| Research Institution | Iwate Medical University |
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Principal Investigator |
HABANO WATARU 岩手医科大学, 薬学部, 准教授 (50332979)
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| Co-Investigator(Renkei-kenkyūsha) |
SUGAI Tamotsu 岩手医科大学, 医学部, 教授 (20187628)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 薬物代謝変動 / エピジェネティクス / DNAメチル化 / 薬物代謝酵素 / 個別化薬物治療 / 腺管分離法 |
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| Outline of Final Research Achievements |
We evaluated the biological significance of DNA methylation in the regulation of drug metabolizing enzyme (DME) genes by genome-wide integrative analysis. Among normal livers, 7 DME genes showed significant inverse correlations between DNA methylation and mRNA expression. In hepatoma cells, treatment with a demethylating agent resulted in upregulation of 5 DME genes, which could be explained by DNA methylation status. Tissue-specific and age-dependent expression of UDP-glucuronosyl transferase 1A splicing variants could be explained by DNA methylation status. Interestingly, some DME genes had unique methylation features similar to those observed in tumor-suppressor or housekeeping genes. Analysis of the DNA methylation landscape facilitated elucidation of the role of DNA methylation.
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Report
(4 results)
Research Products
(6 results)
