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ABCB1 Single-Nucleotide Polymorphisms Determine Tacrolimus Response in Patients With Ulcerative Colitis.
MedLine Citation:
PMID:  21289623     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
K R Herrlinger; H Koc; S Winter; A Teml; E F Stange; K Fellermann; P Fritz; M Schwab; E Schaeffeler
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-02
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  -     ISSN:  1532-6535     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Gastroenterology, Hepatology and Endocrinology, Robert-Bosch-Hospital, Stuttgart, Germany.
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