ABCB1 single-nucleotide polymorphisms determine tacrolimus response in patients with ulcerative colitis
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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.
Projects: G2: Clinical Translation to Non-Invasive Volunteer Setting
Clin. Pharmacol. Ther.
Clin. Pharmacol. Ther. 89(3): 422-8
2nd Feb 2011
K R Herrlinger, H Koc, S Winter, A Teml, E F Stange, K Fellermann, P Fritz, M Schwab, E Schaeffeler
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- Created: 18th Jul 2012 at 12:30
- Last updated: 24th Oct 2013 at 16:19
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