López Lasanta, MaríaMaymó Guarch, JoanAlmirall Bernabé, MiriamMarsal, Sara2015-10-212015-10-212015Lopez-Lasanta M1, Julià A2, Maymó J3, Fernández-Gutierrez B4, Ureña-Garnica I5, Blanco FJ. et al. Variation at interleukin-6 receptor gene is associated to joint damage in rheumatoid arthritis. Arthritis Res Ther. 2015 Sep 4;17:242. doi: 10.1186/s13075-015-0737-8.1478-6354http://hdl.handle.net/10230/24872INTRODUCTION: Interleukin-6 (IL-6) cytokine signaling is key in Rheumatoid Arthritis (RA) pathophysiology. Blocking IL-6 receptor (IL6R) has proven to be a highly effective treatment to prevent joint damage. This study was performed to investigate the association between the genetic variation at IL6R gene and the severity of joint damage in RA. METHODS: IL6R gene tagging SNPs (n = 5) were genotyped in a discovery group of 527 RA patients from 5 different university hospitals from Spain. For each marker, a linear regression analysis was performed using an additive model and adjusting for the years of evolution of the disease, autoantibody status, gender and age. Haplotypes combining the SNPs were also estimated and tested for association with the level of joint destruction. Using an independent cohort of 705 RA patients from 6 university hospitals we performed a validation study of the SNPs associated in the discovery phase. RESULTS: In the discovery group we found a highly significant association between IL6R SNP rs4845618 and the level of joint destruction in RA (P = 0.0058, P corrected = 0.026), and a moderate association with SNP rs4453032 (P = 0.02, P corrected = 0.05). The resulting haplotype from both SNPs was more significantly associated with joint damage (P = 0.0037, P corrected = 0.011). Using the validation cohort, we replicated the association between the two IL-6R SNPs with the degree of joint destruction in RA (P = 0.007 and P = 0.04, meta-analysis P = 0.00011 and P = 0.0021, respectively), and the haplotype association (P = 0.0058, meta-analysis P = 6.64 e-5). CONCLUSIONS: Genetic variation at IL6R gene is associated with joint damage in RA.application/pdfeng© 2015 Lopez-Lasanta et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made/navailable in this article, unless otherwise stated.Artritis reumatoide -- Tractamentinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13075-015-0737-8info:eu-repo/semantics/openAccess