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Evaluation of mutation effects on UDP-glucuronosyltransferase 1A1 activity toward personalized medicine

Research Project

Project/Area Number 21590185
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionKobe Pharmaceutical University

Principal Investigator

TAKEUCHI Atsuko  神戸薬科大学, 薬学部, 准教授 (80154970)

Co-Investigator(Kenkyū-buntansha) TODE Chisato  神戸薬科大学, 薬学部, 講師 (20289036)
杉浦 眞喜子  神戸薬科大学, 薬学部, 准教授 (00098500)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords質量分析 / UGT1A1 / 遺伝子変異 / 酵素活性 / LC/MS / 薬物代謝 / ビリルビン / 新生児 / LC / MS
Research Abstract

UDP-glucuronosyltransferase 1A1(UGT1A1) is the only physiological relevant enzyme in bilirubin glucuronidation. Mutations of the UGT1A1 gene reduce the enzyme activity, leading unconjugated hyperbilirubinemia. Bilirubin has two sites capable of glucuronidation and forms bilirubin mono-and di-glucuronides(BMG and BDG). We constructed the several expression plasmids for UGT1A1 with missense mutation(G71R, F83L, I322V, and G493R) in the gene. In this study, we established the high-throughput quantitative methods for BMG and BDG using UPLC-Orbitrap MS technique, and estimated each glucuronidation capacity of the mutated UGT1A1 by transient transfection and expression.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (17 results)

All 2012 2011 2010 2009

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (12 results)

  • [Journal Article] A polymorphic mutation, c.-3279T>G, in the UGT1A1 promoter is a risk factor for neonatal jaundice in the Malay population2010

    • Author(s)
      Yusoff S., Takeuchi A., Ashi C., Tsukada M., Maamor N. H., Zilfalil B. A., Yusoff N. M., Nakamura T., Hirai M, Harahap I. S., Gunadi, Lee M. J., Nishimura N., Takaoka Y., Morikawa S., Morioka I., Yokoyama N., Matsuo M., Nishio H., van Rostenberghe H.
    • Journal Title

      Pediatr. Res

      Pages: 25-28

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ligand orientation governs conjugation capacity of UDP-glucuronosyltransferase 1A12010

    • Author(s)
      Takaoka Y., Ohta M., Takeuchi A., Miura K., Matsuo M., Sakaeda T
    • Journal Title

      Sugano A., Nishio H., J Biochem

      Pages: 25-28

    • NAID

      10027877025

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ligand orientation governs conjugation capacity of UDP-glucuronosyltransferase 1A12010

    • Author(s)
      Takaoka Yutaka
    • Journal Title

      J.Biochem.

      Volume: 148 Pages: 25-28

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A polymorphic mutation, c.-3279T>G, in the UGT1A1 promoter is a risk factor for neonatal jaundice in the Malay population2010

    • Author(s)
      Surini Yusoff
    • Journal Title

      Pediatr.Res

      Volume: 67 Pages: 401-406

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A polymorphic mutation, c.-3279T>G, in the UGT1A1 promoter is a risk factor for neonatal jaundice in the Malay population.2010

    • Author(s)
      Surini Yusoff
    • Journal Title

      Pediatr. Res (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] UDP-glucuronosyltransferase 1A1の安定発現培養細胞中の酵素活性の測定2012

    • Author(s)
      塚本恵梨, 近江昇一, 竹内敦子, 西尾久英
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] UDP-glucuronosyltransferase 1A1によるビリルビン代謝能の解析2011

    • Author(s)
      近江昇一, 竹内敦子, 和田昭盛, 西尾久英
    • Organizer
      第59回質量分析総合討論会
    • Place of Presentation
      吹田
    • Year and Date
      2011-09-14
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] UDP-glucuronosyltransferase 1A1遺伝子多型抱合能の高分解能質量分析法による測定ビリルビン代謝能の解析2011

    • Author(s)
      近江昇一, 竹内敦子, 和田昭盛, 西尾久英
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-29
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] UDP-glucuronosyltransferase 1A1遺伝子の転写に関与する因子の解析2010

    • Author(s)
      竹内敦子, 葭ちとせ, 西尾久英
    • Organizer
      第58回質量分析学会/第1回アジア・オセアニア質量分析会議
    • Place of Presentation
      つくば
    • Year and Date
      2010-06-17
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] UDP-glucuronosyltransferase 1A1(UGT1A1)遺伝子の転写調節領域における変異が転写活性に及ぼす影響2010

    • Author(s)
      葭ちとせ, 竹内敦子, 和田昭盛, 西尾久英
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-28
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] グルクロン酸転移反応の分子シミュレーション解析と抱合能予測2009

    • Author(s)
      高岡裕
    • Organizer
      第32回日本分子生物学会大会
    • Place of Presentation
      横浜・パシフィコ横浜
    • Year and Date
      2009-12-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] UDP-グルクロン酸転移酵素の抱合反応の分子シミュレーション解析2009

    • Author(s)
      高岡裕
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸・国際会議場
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] Analysis of UDP-glucuronosyltransferase 1A1 capacity2009

    • Author(s)
      Takeuchi A., Tsukada M., Nishio H
    • Organizer
      18th International Mass Spectrometry Conference
    • Place of Presentation
      Brenmen
    • Year and Date
      2009-09-02
    • Related Report
      2011 Final Research Report
  • [Presentation] Analysis of UDP-glucuronosyltransferase 1A1 capacity2009

    • Author(s)
      竹内敦子
    • Organizer
      18th International Mass Spectrometry Conference
    • Place of Presentation
      ドイツ・ブレーメン
    • Year and Date
      2009-09-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] UDP-Glucuronosyltaransferase 1A1のグルクロン酸抱合能の解析研究2009

    • Author(s)
      竹内敦子
    • Organizer
      第57回日本質量分析総合討論会
    • Place of Presentation
      大阪・国際会議場
    • Year and Date
      2009-05-15
    • Related Report
      2009 Annual Research Report
  • [Presentation] UDP-Glucuronosyltaransferase 1A1のグルクロン酸抱合能の解析研究2009

    • Author(s)
      竹内敦子, 塚田雅子, 西尾久英
    • Organizer
      第57回日本質量分析総合討論会
    • Place of Presentation
      大阪
    • Year and Date
      2009-05-12
    • Related Report
      2011 Final Research Report
  • [Presentation] In silico estimation for the conjugation capacity of mutant UDP-glucuronosyltransferase 1A1.2009

    • Author(s)
      Yutaka Takaoka
    • Organizer
      The 10th International Conference Bioinfo2009
    • Place of Presentation
      韓国・釜山
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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