ZNF133 Is Associated with Infliximab Responsiveness in Patients with Inflammatory Bowel Diseases.

Eun Suk Jung, Ko-Woon Choi, Seung Won Kim, Matthias Hübenthal, Sören Mucha, Jihye Park, Zewon Park, David Ellinghaus, Stefan Schreiber, Andre Franke, Woo Yong Oh, Jae Hee Cheon
Year of publication:
Journal title abbreviated:
J. Gastroenterol. Hepatol.
Journal title long:
Journal of gastroenterology and hepatology
Impact factor:
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: (1) primary response vs. nonresponse and (2) 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 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 loss of infliximab response. In multivariate regression analysis, rs2228273 (P = 2.10 × 10-5 ), concurrent azathioprine/6-mercaptopurine use, and body weight 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 loss of response in patients with Crohn's disease. CONCLUSIONS:We identified clinical and genetic markers associated with infliximab response in inflammatory bowel disease patients. Our findings could provide insights to maximize the efficacy of infliximab therapy in IBD patients.