RT Journal Article
T1 Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis.
A1 Márquez, Ana
A1 Ferreiro-Iglesias, Aida
A1 Dávila-Fajardo, Cristina L
A1 Montes, Ariana
A1 Pascual-Salcedo, Dora
A1 Perez-Pampin, Eva
A1 Moreno-Ramos, Manuel J
A1 García-Portales, Rosa
A1 Navarro, Federico
A1 Moreira, Virginia
A1 Magro, César
A1 Caliz, Rafael
A1 Ferrer, Miguel Angel
A1 Alegre-Sancho, Juan José
A1 Joven, Beatriz
A1 Carreira, Patricia
A1 Balsa, Alejandro
A1 Vasilopoulos, Yiannis
A1 Sarafidou, Theologia
A1 Cabeza-Barrera, José
A1 Narvaez, Javier
A1 Raya, Enrique
A1 Cañete, Juan D
A1 Fernández-Nebro, Antonio
A1 Ordóñez, María del Carmen
A1 de la Serna, Arturo R
A1 Magallares, Berta
A1 Gomez-Reino, Juan J
A1 González, Antonio
A1 Martín, Javier
K1 Antirreumáticos
K1 Artritis reumatoide
K1 Estudio de asociación del genoma completo
K1 Genotipo
K1 Polimorfismo de nucleótido simple
K1 Resultado del tratamiento
K1 Factor de necrosis tumoral alfa
AB INTRODUCTIONIn this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations.METHODSThe four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients.RESULTSNone of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis.CONCLUSIONOur data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.
PB BioMed Central
SN 1478-6354
YR 2014
FD 2014-03-11
LK http://hdl.handle.net/10668/2316
UL http://hdl.handle.net/10668/2316
LA en
NO Márquez A, Ferreiro-Iglesias A, Dávila-Fajardo CL, Montes A, Pascual-Salcedo D, Perez-Pampin E, et al. Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis. Arthritis Res. Ther. 2014; 16(2):R66
NO Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 8, 2025