ABCB1 Single-Nucleotide Polymorphisms Determine Tacrolimus Response in Patients With Ulcerative Colitis

作者：Herrlinger K R^*; Koc H; Winter S; Teml A; Stange E F; Fellermann K; Fritz P; Schwab M; Schaeffeler E

来源：Clinical Pharmacology & Therapeutics, 2011, 89(3): 422-428.

DOI：10.1038/clpt.2010.348

Tacrolimus (Tac) is effective in the treatment of steroid-refractory ulcerative colitis (UC); however, nonresponse and unpredictable side effects are major limitations. Because Tac response in patients who have undergone solid-organ transplantation has been associated with the presence of variants in CYP3A and ABCB1, we elucidated the contributions of CYP3A4*1B and CYP3A5*3 and of ABCB1 1236C>T, 2677G>T, A, and 3435C>T polymorphisms to Tac response in 89 patients with UC. Short-term remission and response were achieved in 61 and 14% of the patients, respectively, and were associated with colectomy-free survival. In a linear logistic regression model, patients with homozygous variants for one of the three ABCB1 alleles showed significantly higher short-term remission rates as compared with those of other genotypes. The effects held true after multivariate analysis including multiple comparisons and were more pronounced after correction for dose-adjusted Tac blood trough levels. We suggest that ABCB1, but not CYP3A5, may predict short-term remission of Tac in steroid-refractory UC.

• 出版日期2011-3