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. 2019 Dec;34(12):2118-2125.
doi: 10.1111/jgh.14696. Epub 2019 Jun 18.

Association of TRAP1 with infliximab-induced mucosal healing in Crohn's disease

Sang Hyoung Park  1 , Myunghee Hong  2 , Ho-Su Lee  2 , Byong Duk Ye  1 , Sung Wook Hwang  1 , Seulgi Jung  2 , Jiwon Baek  2 , Jung Won Moon  2 , Byoung Mok Kim  2 , Seak Hee Oh  3 , Kyung Mo Kim  3 , Inchul Lee  4 , Chang-Nim Im  5 , Jianjun Liu  6 , Dermot P B McGovern  7 , Suk-Kyun Yang  1 , Kyuyoung Song  2
Affiliations

Association of TRAP1 with infliximab-induced mucosal healing in Crohn's disease

Sang Hyoung Park et al. J Gastroenterol Hepatol. 2019 Dec.

Abstract

Background and aim: Anti-tumor necrosis factor (TNF) agents, such as infliximab (IFX), have been increasingly used to induce and maintain disease remission in patients with Crohn's disease (CD). Despite a considerable non-response rate, little is known about the genetic predictors of response to anti-TNF therapy in CD. Our aim in this study was to investigate the genetic factors associated with response to anti-TNF therapy in patients with CD.

Methods: We performed a two-stage genome-wide association study (GWAS) to identify loci influencing the response to IFX among Korean patients with CD, comprising 42 good responders with mucosal healing and 70 non-responders. The achievement of mucosal healing was assessed by endoscopy and imaging. The functional significance of TRAP1 (TNF receptor associated protein 1) was examined using dextran sodium sulfate-induced colitis model in TRAP1 transgenic mice.

Results: The GWAS identified rs2158962, an intronic single nucleotide polymorphism (SNP) of TRAP1, significantly associated with mucosal healing (odds ratio = 4.94; Pcombined = 1.35 × 10-7 ). In the dextran sodium sulfate-induced acute colitis, TRAP1 transgenic mice showed a better response to IFX than the wild-type mice.

Conclusions: The TRAP1 gene is associated with mucosal healing in CD patients following IFX therapy. Identifying the genetic predictors of mucosal healing to anti-TNF therapy can prevent patients from exposure to ineffective therapies.

Keywords: Crohn's disease; TRAP1; infliximab; response.

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