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oai:repisalud.isciii.es:20.500.12105/170972024-11-28T15:09:08Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16980col_20.500.12105_16985col_20.500.12105_16987

00925njm 22002777a 4500 dc Lopez-Lasanta, Maria author Julià, Antonio author Maymó, Joan author Fernández-Gutierrez, Benjamín author Ureña-Garnica, Inmaculada author Blanco, Francisco J author Cañete, Juan D author Alperi-López, Mercedes author Olivè, Alex author Corominas, Héctor author Tornero, Jesus author Erra, Alba author Almirall, Miriam author Palau, Nuria author Ortiz, Ana author Avila, Gabriela author Rodriguez-Rodriguez, Luis author Alonso, Arnald author Tortosa, Raül author Gonzalez-Alvaro, Isidoro author Marsal, Sara author 2015-09-04 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. 10.1186/s13075-015-0737-8 1478-6362 1478-6354 Arthritis Research & Therapy http://hdl.handle.net/10668/2272 26336855 http://hdl.handle.net/20.500.12105/17097 Artritis reumatoide Alelos Estudios de cohortes Frecuencia génica Predisposición genética a la enfermedad Genotipo Halotipos Articulaciones Modelos lineales Desequilibrio de ligamiento Metanálisis como asunto Polimorfismo de nucleótido único Receptores de interleucina-6 España Variation at interleukin-6 receptor gene is associated to joint damage in rheumatoid arthritis.