RT Journal Article
T1 Variation at FCGR2A and functionally related genes is associated with the response to anti-TNF therapy in rheumatoid arthritis.
A1 Avila-Pedretti, Gabriela
A1 Tornero, Jesús
A1 Fernández-Nebro, Antonio
A1 Blanco, Francisco
A1 González-Alvaro, Isidoro
A1 Cañete, Juan D
A1 Maymó, Joan
A1 Alperiz, Mercedes
A1 Fernández-Gutiérrez, Benjamín
A1 Olivé, Alex
A1 Corominas, Héctor
A1 Erra, Alba
A1 Aterido, Adrià
A1 López Lasanta, María
A1 Tortosa, Raül
A1 Julià, Antonio
A1 Marsal, Sara
K1 Antirreumáticos
K1 Macrófagos
K1 Polimorfismo de nucleótido único
K1 Artritis reumatoide
K1 Receptores de IgG
K1 Líquido sinovial
K1 Resultado del tratamiento
K1 Factor de necrosis tumoral alfa
AB OBJECTIVEAnti-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.METHODSA 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.RESULTSWe 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).CONCLUSIONSIn 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.
PB Public Library of Science
YR 2015
FD 2015-04-07
LK http://hdl.handle.net/10668/2268
UL http://hdl.handle.net/10668/2268
LA en
NO 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; 10(4):e0122088
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 7, 2025