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

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

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.

CROHN'S disease; HEALING; SINGLE nucleotide polymorphisms; TUMOR necrosis factor receptors; TRANSGENIC mice; FRACTURE healing

Journal of Gastroenterology & Hepatology, 2019, Vol 34, Issue 12, p2118

0815-9319

Academic Journal

10.1111/jgh.14696