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Analysis of epigenetic mechanisms on the regulation of drug metabolizing enzymes and its application to personalized drug therapy

Research Project

Project/Area Number 24590451
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionIwate Medical University

Principal Investigator

HABANO WATARU  岩手医科大学, 薬学部, 准教授 (50332979)

Co-Investigator(Renkei-kenkyūsha) SUGAI Tamotsu  岩手医科大学, 医学部, 教授 (20187628)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
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)
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
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.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (6 results)

All 2014 2013 2012

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results) (of which Invited: 3 results)

  • [Journal Article] An aryl hydrocarbon receptor induces VEGF expression through ATF4 under glucose deprivation in HepG22013

    • Author(s)
      Terashima J, Tachikawa C, Kudo K, Habano W, Ozawa S
    • Journal Title

      BMC Mol Biol. 2013 Dec 12;14:27

      Volume: 14 Issue: 1 Pages: 27-27

    • DOI

      10.1186/1471-2199-14-27

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] DNAメチル化機構に着目した薬物代謝変動要因の探索2014

    • Author(s)
      幅野渉、小澤正吾
    • Organizer
      日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] オミクス情報を活用した薬物代謝変動要因の探索2014

    • Author(s)
      幅野渉
    • Organizer
      日本臨床検査医学会東北支部総会
    • Place of Presentation
      盛岡
    • Year and Date
      2014-08-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 薬物動態関連遺伝子のエピジェネティックな発現制御:プロモーターメチル化を中心に2013

    • Author(s)
      幅野渉、小澤正吾
    • Organizer
      日本薬物動態学会第28回年会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] エピジェネティックメカニズムによる薬物代謝酵素遺伝子発現調節2012

    • Author(s)
      幅野渉
    • Organizer
      日本薬学会東北支部総会・学術講演会
    • Place of Presentation
      仙台
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Epigenetic regulation of the UGT1A1 gene expression in hepatocellular carcinoma cells.2012

    • Author(s)
      幅野渉、三浦僚、丸本慎太郎、佐野祐子、寺島潤、蒲生俊恵、小澤正吾
    • Organizer
      第27回日本薬物動態学会
    • Place of Presentation
      千葉
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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