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Variation in Interleukin 6 Receptor Gene Associates with Risk of Crohn’s Disease and Ulcerative Colitis

Parisinos, CA; Serghiou, S; Katsoulis, M; George, MJ; Patel, RS; Hemingway, H; Hingorani, AD; (2018) Variation in Interleukin 6 Receptor Gene Associates with Risk of Crohn’s Disease and Ulcerative Colitis. Gastroenterology , 155 (2) pp. 303-306. 10.1053/j.gastro.2018.05.022. Green open access

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Abstract

Interleukin 6 (IL6) is an inflammatory cytokine; signaling via its receptor (IL6R) is believed to contribute to development of inflammatory bowel diseases (IBD). The single nucleotide polymorphism rs2228145 in IL6R associates with increased levels of soluble IL6R (s-IL6R), as well as reduced IL6R signaling and risk of inflammatory disorders; its effects are similar to those of a therapeutic monoclonal antibody that blocks IL6R signaling. We used the effect of rs2228145 on s-IL6R level as an indirect marker to investigate whether reduced IL6R signaling associates with risk of ulcerative colitis (UC) or Crohn’s disease (CD). In a genome-wide meta-analysis of 20,550 patients with CD, 17647 patients with UC, and more than 40,000 individuals without IBD (controls), we found that rs2228145 (scaled to a 2-fold increase in s-IL6R) was associated with reduced risk of CD (odds ratio, 0.876; 95% CI, 0.822–0.933; P=.00003) or UC (odds ratio, 0.932; 95% CI, 0.875–0.996; P=.036). These findings indicate that therapeutics designed to block IL6R signaling might be effective in treatment of IBD.

Type: Article
Title: Variation in Interleukin 6 Receptor Gene Associates with Risk of Crohn’s Disease and Ulcerative Colitis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1053/j.gastro.2018.05.022
Publisher version: https://www.gastrojournal.org/article/S0016-5085(1...
Language: English
Additional information: © 2018 by the AGA Institute. This is an Open Access article published under the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Keywords: SNP, Genetics, Mendelian randomization, Drug target validation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: https://discovery.ucl.ac.uk/id/eprint/10049377
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