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論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases.
掲載誌名	正式名：Intestinal research 略　 称：Intest Res ISSNコード：1598-9100(Print)1598-9100(Linking)
掲載区分	国内
巻・号・頁	15(3),pp.328-337
著者・共著者	Sato Toshiyuki, Takagawa Tetsuya, Kakuta Yoichi, Nishio Akihiro, Kawai Mikio, Kamikozuru Koji, Yokoyama Yoko, Kita Yuko, Miyazaki Takako, Iimuro Masaki, Hida Nobuyuki, Hori Kazutoshi, Ikeuchi Hiroki, Nakamura Shiro
発行年月	2017/07
概要	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 detailin 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 (<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 thiopurine-induced 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.
DOI	10.5217/ir.2017.15.3.328
PMID	28670229