Variation at FCGR2A and Functionally Related Genes Is Associated with the Response to Anti-TNF Therapy in Rheumatoid Arthritis

Avila Pedretti, Gabriela; Tornero, Jesús; Fernández-Nebro, Antonio; Blanco, Francisco; González-Alvaro, Isidoro; Cañete Crespillo, Juan de Dios; Maymó Guarch, Joan; Alperiz, Mercedes; Fernández-Gutiérrez, Benjamín; Olivé, Alex; Corominas, Héctor; Erra, Alba; Aterido Ballonga, Adrià, 1990-; López Lasanta, María; Tortosa, Raül; Julià, Antonio; Marsal, Sara

Variation at FCGR2A and Functionally Related Genes Is Associated with the Response to Anti-TNF Therapy in Rheumatoid Arthritis

Mostra el registre complet Registre parcial de l'ítem

dc.contributor.author Avila Pedretti, Gabrielaca
dc.contributor.author Tornero, Jesúsca
dc.contributor.author Fernández-Nebro, Antonioca
dc.contributor.author Blanco, Franciscoca
dc.contributor.author González-Alvaro, Isidoroca
dc.contributor.author Cañete Crespillo, Juan de Diosca
dc.contributor.author Maymó Guarch, Joanca
dc.contributor.author Alperiz, Mercedesca
dc.contributor.author Fernández-Gutiérrez, Benjamínca
dc.contributor.author Olivé, Alexca
dc.contributor.author Corominas, Héctorca
dc.contributor.author Erra, Albaca
dc.contributor.author Aterido Ballonga, Adrià, 1990-ca
dc.contributor.author López Lasanta, Maríaca
dc.contributor.author Tortosa, Raülca
dc.contributor.author Julià, Antonioca
dc.contributor.author Marsal, Saraca
dc.date.accessioned 2015-05-25T11:13:09Z
dc.date.available 2015-05-25T11:13:09Z
dc.date.issued 2015
dc.description.abstract OBJECTIVE: Anti-TNF therapies have been highly efficacious in the management of rheumatoid arthritis (RA), but 25-30% of patients do not show a significant clinical response. There is increasing evidence that genetic variation at the Fc receptor FCGR2A is associated with the response to anti-TNF therapy. We aimed to validate this genetic association in a patient cohort from the Spanish population, and also to identify new genes functionally related to FCGR2A that are also associated with anti-TNF response. METHODS: A total of 348 RA patients treated with an anti-TNF therapy were included and genotyped for FCGR2A polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was tested for association globally and independently for each anti-TNF drug (infliximab, etanercept and adalimumab). Using gene expression profiles from macrophages obtained from synovial fluid of RA patients, we searched for genes highly correlated with FCGR2A expression. Tag SNPs were selected from each candidate gene and tested for association with the response to therapy. RESULTS: We found a significant association between FCGR2A and the response to adalimumab (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also found a significant association between FCGR2A and the response to infliximab (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with FCGR2A expression in RA synovial fluid macrophages (P<0.001). We found a significant association between the genetic variation at DHX32 (rs12356233, corrected P=0.019) and a nominally significant association between RGS12 and the response to adalimumab (rs4690093, uncorrected P=0.040). In the anti-CCP positive group of patients, we also found a nominally significant association between RGS12 and the response to infliximab (rs2857859, uncorrected P=0.042). CONCLUSIONS: In the present study we have validated the FCGR2A association in an independent population, and we have identified new genes associated with the response to anti-TNF therapy in RA.ca
dc.format.mimetype application/pdfca
dc.identifier.citation Avila-Pedretti G, Tornero J, Fernández-Nebro A, Blanco F, González-Alvaro I, Cañete JD. et al. Variation at FCGR2A and Functionally Related Genes Is Associated with the Response to Anti-TNF Therapy in Rheumatoid Arthritis. PLoS One. 2015 Apr 7;10(4):e0122088. doi: 10.1371/journal.pone.0122088. eCollection 2015.ca
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0122088
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/23649
dc.language.iso engca
dc.publisher Public Library of Scienceca
dc.relation.ispartof PLoS One. 2015 Apr 7;10(4):e0122088
dc.rights © 2015 Avila-Pedretti et al. This is anopen access article distributed under the terms of the http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source arecreditedca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
dc.subject.other Artritis reumatoideca
dc.title Variation at FCGR2A and Functionally Related Genes Is Associated with the Response to Anti-TNF Therapy in Rheumatoid Arthritisca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

Col·leccions

Articles (Hospital del Mar Research Institute)