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ZNF133 is associated with infliximab responsiveness in patients with inflammatory bowel diseases

Authors
 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 
Citation
 JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Vol.34(10) : 1727-1735, 2019 
Journal Title
 JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 
ISSN
 0815-9319 
Issue Date
2019
Keywords
inflammatory bowel disease ; infliximab response ; whole-exome sequencing
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.
Full Text
https://onlinelibrary.wiley.com/doi/full/10.1111/jgh.14652
DOI
10.1111/jgh.14652
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Kim, Seung Won(김승원) ORCID logo https://orcid.org/0000-0002-1692-1192
Park, Ji Hye(박지혜)
Jung, Eun Suk(정은석)
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175176
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