論文

査読有り
2017年

NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases

Intestinal Research
  • Toshiyuki Sato
  • ,
  • Tetsuya Takagawa
  • ,
  • Yoichi Kakuta
  • ,
  • Akihiro Nishio
  • ,
  • Mikio Kawai
  • ,
  • Koji Kamikozuru
  • ,
  • Yoko Yokoyama
  • ,
  • Yuko Kita
  • ,
  • Takako Miyazaki
  • ,
  • Masaki Iimuro
  • ,
  • Nobuyuki Hida
  • ,
  • Kazutoshi Hori
  • ,
  • Hiroki Ikeuchi
  • ,
  • Shiro Nakamura

15
3
開始ページ
328
終了ページ
337
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.5217/ir.2017.15.3.328
出版者・発行元
Korean Association for the Study of Intestinal Diseases

Background/Aims: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD). Methods: One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing. Results: None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early ( &lt
8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined. Conclusions: Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurineinduced leukopenia and severe hair loss
therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.

リンク情報
DOI
https://doi.org/10.5217/ir.2017.15.3.328
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28670229

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