ATP-binding cassette subfamily B member 1 1236C/T polymorphism significantly affects the therapeutic outcome of tacrolimus in patients with refractory ulcerative colitis

Motoyuki Onodera, Katsuya Endo, Yoichi Kakuta, Masatake Kuroha, Tomoya Kimura, Keiichiro Hiramoto, Yoshitake Kanazawa, Kenichi Negoro, Hisashi Shiga, Yoshitaka Kinouchi, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Background and Aim: Tacrolimus is now considered to be one of the main therapeutic options for refractory ulcerative colitis. Both cytochrome P-450 3A5 (CYP3A5) and ATP-binding cassette subfamily B member 1 (ABCB1) associated with tacrolimus metabolism are known to have several genetic polymorphisms. However, it remains controversial whether these polymorphisms affect the therapeutic efficacy for ulcerative colitis. We aimed to investigate the influence of both CYP3A5 and ABCB1 polymorphisms on the efficacy of tacrolimus in ulcerative colitis treatment under the tight dose-adjusting strategy. Methods: Sixty-one Japanese patients with ulcerative colitis treated with tacrolimus were enrolled retrospectively. Tacrolimus treatment was performed using the tight dose-adjusting strategy. Genotyping for CYP3A5*3, ABCB1 1236C>T, 2677G>A,T, and 3435C>T were performed, and the clinical outcomes at 12 weeks after the initiation of tacrolimus were compared among the genotypes. Results: There was no association between the CYP3A5 genotypes and therapeutic efficacy. In contrast, a significant association was observed with the ABCB1 1236C > T polymorphism and therapeutic efficacy. The ABCB1 1236CC+CT groups (n = 41) had a significantly higher response rate (73% vs 35%; P = 0.004) and remission rate (61% vs 20%; P = 0.002) than the TT group (n = 20). The multivariate logistic regression analysis also revealed that ABCB1 1236C>T was identified as an independent factor associated with remission. Conclusions: ABCB1 1236C>T polymorphism significantly affects the therapeutic efficacy of tarcolimus at 12 weeks under the tight dose-adjusting treatment for ulcerative colitis.

Original languageEnglish
Pages (from-to)1562-1569
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume32
Issue number9
DOIs
Publication statusPublished - 2017 Sep

Keywords

  • ABCB1
  • CYP
  • tacrolimus
  • ulcerative colitis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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