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The examination about the usefulness of SLC38A9 as genetic biomarker to predict blood concentration of azathioprine.

Research Project

Project/Area Number 24590665
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

UCHIYAMA Kazuhiko  京都府立医科大学, 医学(系)研究科(研究院), 助教 (50298428)

Co-Investigator(Kenkyū-buntansha) NAITO Yuji  京都府立医科大学, 医学研究科, 准教授 (00305575)
TAKAGI Tomohisa  京都府立医科大学, 医学研究科, 准教授 (70405257)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsazathioprine / 6-TGN / genetic biomarker / azathioprine(AZA) / SLC38A9 / EAI / Express Genotyping / アザチオプリン
Outline of Final Research Achievements

Azathioprine (AZA) is widely used for the treatment of inflammatory bowel disease (IBD) patients. In this study, single nucleotide polymorphisms (SNPs) related to differential gene expression affecting AZA drug metabolism in combination therapy with 5-ASA were examined.
To identify genetic biomarkers for the prediction of 6-TGN blood concentration, ExpressGenotyping analysis, which is able to detect critical pharmacogenetic SNPs by analyzing drug-induced expression allelic imbalance (EAI) of premature RNA, was used. Both in HapMap lymphocytes, and blood samples on 38 patients with inflammatory bowel disease treated with AZA, corroboration of the obtained SNPs was attempted. Among them, SNPs within SLC38A9 showed a particular correlation with patients’ 6-TGN blood concentrations. This study provides helpful information on genetic biomarkers for optimized AZA/5-ASA treatment of IBD patients.

Report

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

    (9 results)

All 2014 2013 2012 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (7 results)

  • [Journal Article] New genetic biomarkers predicting azathioprine blood concentrations in combination therapy with 5-aminosalicylic acid.2014

    • Author(s)
      Uchiyama K, Takagi T, Iwamoto Y, Kondo N, Okayama T, Yoshida N, Kamada K, Katada K, Handa O, Ishikawa T, Yasuda H, Sakagami J, Konishi H, Yagi N, Naito Y, Itoh Y.
    • Journal Title

      PLoS One

      Volume: 9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] New genetic biomarkers predicting azathioprine blood concentrations in combination therapy with 5-aminosalicylic Acid.2014

    • Author(s)
      Uchiyama K, Takagi T, Iwamoto Y, Kondo N, Okayama T, Yoshida N, Kamada K, Katada K, Handa O, Ishikawa T, Yasuda H, Sakagami J, Konishi H, Yagi N, Naito Y, Itoh Y
    • Journal Title

      PLoS One

      Volume: 24;9(4) Issue: 4 Pages: e95080-e95080

    • DOI

      10.1371/journal.pone.0095080

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Enhancement of colonic mucosal repair and protection by FGF15/19 derived from myofibroblasts2013

    • Author(s)
      Kazuhiko Uchiyama, Yuji Naito, Tomohisa Takagi, Wataru Fukuda, Kazuhiro Katada, Kazuhiro Kamada, Osamu Handa, Nobuaki Yagi, Toshikazu Yoshikawa
    • Organizer
      16th International Congress of Mucosal Immunology (ICMI 2013)
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] Azathioprine血中濃度予測バイオマーカーとしてのSLC38A9遺伝子多型の有用性に関する解析2013

    • Author(s)
      内山和彦、高木智久、堅田和弘、鎌田和浩、半田 修、保田宏明、阪上順一、小西英幸、八木信明、内藤裕二、伊藤義人
    • Organizer
      第50回日本消化器免疫学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Allele解析をもとにしたSLC38A9の遺伝子多型と炎症性腸疾患の治療におけるazathioprineの薬物代謝に関する検討2013

    • Author(s)
      内山和彦
    • Organizer
      第99回日本消化器病学会総会
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Research-status Report
  • [Presentation] Allele解析によって明らかとなったSLC38A9の遺伝子多型と炎症性腸疾患の治療におけるazathioprineの薬物代謝に関する検討2013

    • Author(s)
      内山和彦
    • Organizer
      第50回日本臨床分子医学会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Investigation of new biomarker for diagnosis of colorectal cancer ; the usability of F marker;2012

    • Author(s)
      内山和彦
    • Organizer
      第20回欧州消化器病週間(UEGW 2012)
    • Place of Presentation
      Amsterdam
    • Related Report
      2012 Research-status Report
  • [Presentation] Identification of New Genetic Biomarkers Predicting the Azathioprine Blood Concentration with 5-aminosalicylic acid as Combination Therapy for Inflammatory Bowel Disease

    • Author(s)
      Kazuhiko Uchiyama, Yuji Naito, Tomohisa Takagi, Yasunori Iwamoto, Yasuhisa Nemoto, Kazuhiro Katada, Kazuhiro Kamada, Osamu Handa, Hiroaki Yasuda, Junichi Sakagami, Hideyuki Konishi, Nobuaki Yagi, Toshikazu Yoshikawa
    • Organizer
      The 1st Annual Meeting of AOCC
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Allele解析によって明らかとなったSLC38A9の遺伝子多型と炎症性腸疾患の治療におけるazathioprineの薬物代謝に関する検討

    • Author(s)
      内山和彦、内藤裕二、高木智久、堅田和弘、鎌田和浩、半田 修、保田宏明、阪上順一、小西英幸、八木信明、伊藤義人
    • Organizer
      第50回日本臨床分子医学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report

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

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