Author information

1 Institute of Health Informatics Research, Faculty of Population Health Sciences University College London 222 Euston Road United Kingdom NW1 2DA. Electronic address: c.parisinos@ucl.ac.uk.

2 Health Research and Policy, Epidemiology Stanford University 450 Serra Mall Stanford United States of America CA 94305 - 2004.

3 Institute of Health Informatics Research, Faculty of Population Health Sciences University College London 222 Euston Road United Kingdom NW1 2DA.

4 Centre for Clinical Pharmacology, Division of Medicine, University College London, Gower Street, United Kingdom, WC1E 6BT.

5 Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, 222 Euston Road, United Kingdom, NW1 2DA.

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.