RT Journal Article
T1 Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept.
A1 Ferreiro-Iglesias, Aida
A1 Montes, Ariana
A1 Perez-Pampin, Eva
A1 Cañete, Juan D
A1 Raya, Enrique
A1 Magro-Checa, Cesar
A1 Vasilopoulos, Yiannis
A1 Caliz, Rafael
A1 Ferrer, Miguel Angel
A1 Joven, Beatriz
A1 Carreira, Patricia
A1 Balsa, Alejandro
A1 Pascual-Salcedo, Dora
A1 Blanco, Francisco J
A1 Moreno-Ramos, Manuel J
A1 Manrique-Arija, Sara
A1 Ordoñez, María Del Carmen
A1 Alegre-Sancho, Juan Jose
A1 Narvaez, Javier
A1 Navarro-Sarabia, Federico
A1 Moreira, Virginia
A1 Valor, Lara
A1 Garcia-Portales, Rosa
A1 Marquez, Ana
A1 Gomez-Reino, Juan J
A1 Martin, Javier
A1 Gonzalez, Antonio
K1 Pharmacogenomic Testing
K1 Pharmacogenomic Variants
K1 Polymorphism, Single Nucleotide
K1 Tumor Necrosis Factor-alpha
AB Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs.
PB Public Library Of Science
YR 2019
FD 2019-02-28
LK http://hdl.handle.net/10668/13641
UL http://hdl.handle.net/10668/13641
LA en
NO Ferreiro-Iglesias A, Montes A, Perez-Pampin E, Cañete JD, Raya E, Magro-Checa C, et al. Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept. PLoS One. 2019 Feb 28;14(2):e0213073
NO This work was supported by the Instituto de Salud Carlos III (ISCIII, Spain) through grants PI14/01651, PI17/01606 and RD16/0012/0014 to AGandPI12/01909 to JJG-R. These grants are partially financed by the European Regional Development Fund of the EU (FEDER)
DS RISalud
RD Apr 19, 2025