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ATP‐binding cassette subfamily B member 1 1236C/T polymorphism significantly affects the therapeutic outcome of tacrolimus in patients with refractory ulcerative colitis
Author(s) -
Onodera Motoyuki,
Endo Katsuya,
Kakuta Yoichi,
Kuroha Masatake,
Kimura Tomoya,
Hiramoto Keiichiro,
Kanazawa Yoshitake,
Negoro Kenichi,
Shiga Hisashi,
Kinouchi Yoshitaka,
Shimosegawa Tooru
Publication year - 2017
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13753
Subject(s) - ulcerative colitis , tacrolimus , medicine , gastroenterology , cyp3a5 , genotype , transplantation , disease , biology , biochemistry , gene
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.