Variation at interleukin-6 receptor gene is associated to joint damage in rheumatoid arthritis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Maria Lopez-Lasanta, Antonio Julià, Joan Maymó, Benjamín Fernández-Gutierrez, Inmaculada Ureña-Garnica, Francisco J. Blanco, Juan D. Cañete, Mercedes Alperi-López, Alex Olivè, Héctor Corominas, Jesus Tornero, Alba Erra, Miriam Almirall, Nuria Palau, Ana Ortiz, Gabriela Avila, Luis Rodriguez-Rodriguez, Arnald Alonso, Raül Tortosa, Isidoro Gonzalez-Alvaro, Sara Marsal

ABSTRACT

INTRODUCTION: 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. More... »

PAGES

242

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13075-015-0737-8

DOI

http://dx.doi.org/10.1186/s13075-015-0737-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052920392

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26336855


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