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ZNF133 is associated with infliximab responsiveness in patients with inflammatory bowel diseases
Author(s) -
Jung Eun Suk,
Choi Kowoon,
Kim Seung Won,
Hübenthal Matthias,
Mucha Sören,
Park Jihye,
Park Zewon,
Ellinghaus David,
Schreiber Stefan,
Franke Andre,
Oh Woo Yong,
Cheon Jae Hee
Publication year - 2019
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.14652
Subject(s) - infliximab , medicine , inflammatory bowel disease , azathioprine , crohn's disease , ulcerative colitis , logistic regression , gastroenterology , disease
Abstract Background and Aim Infliximab has been widely prescribed for treating inflammatory bowel disease (IBD). However, the response rates to infliximab differ among patients. Therefore, we aimed to identify the genetic and clinical markers that predict infliximab response. Methods A total of 139 Korean patients with IBD who received infliximab were classified according to infliximab response as follows: (i) primary response vs nonresponse and (ii) sustained response vs loss of response. We performed an association study using whole‐exome sequencing data to identify genetic variants associated with infliximab response. Candidate variants were validated in 77 German patients with IBD. Stepwise multivariate logistic regression was performed to identify predictors. Results We found five candidate variants that were associated with primary nonresponse to infliximab ( P < 5 × 10 −6 ). Of the five variants, rs2228273 in ZNF133 was validated in German (combined P = 6.49 × 10 −7 ). We also identified the best genetic variant (rs9144, P = 4.60 × 10 −6 ) associated with the loss of infliximab response. In multivariate regression analysis, rs2228273 ( P = 2.10 × 10 −5 ), concurrent azathioprine/6‐mercaptopurine use, and bodyweight at the first infliximab use (< 50 kg) were associated with primary nonresponse. In addition, the Crohn's disease activity index at the first infliximab use and rs9144 ( P = 0.001) were independently associated with the loss of response in patients with Crohn's disease. Conclusions We identified clinical and genetic markers associated with infliximab response in IBD patients. Our findings could provide insights to maximize the efficacy of infliximab therapy in IBD patients.