Premium
ABCB1 Single‐Nucleotide Polymorphisms Determine Tacrolimus Response in Patients With Ulcerative Colitis
Author(s) -
Herrlinger KR,
Koc H,
Winter S,
Teml A,
Stange EF,
Fellermann K,
Fritz P,
Schwab M,
Schaeffeler E
Publication year - 2011
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2010.348
Subject(s) - ulcerative colitis , tacrolimus , cyp3a5 , gastroenterology , medicine , colectomy , single nucleotide polymorphism , logistic regression , trough level , pharmacogenetics , genotype , pharmacology , transplantation , biology , gene , disease , genetics
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. Clinical Pharmacology & Therapeutics (2011) 89 3, 422–428. doi: 10.1038/clpt.2010.348