title: ATP-binding cassette subfamily B member 1 1236C/T polymorphism significantly affects the therapeutic outcome of tacrolimus in patients with refractory ulcerative colitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Onodera
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Endo
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kakuta
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Kuroha
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Hiramoto
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Kanazawa
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Negoro
authors.affiliation: Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shiga
authors.affiliation: Health Administration Center, Center for the Advancement of Higher Education, Tohoku University, Sendai, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kinouchi
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
keywords: ABCB1; CYP; tacrolimus; ulcerative colitis