Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept

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dc.contributor.author Ferreiro-Iglesias, Aida
dc.contributor.author Montes, Ariana
dc.contributor.author Perez-Pampin, Eva
dc.contributor.author Cañete, Juan D.
dc.contributor.author Raya, Enrique
dc.contributor.author Magro-Checa, Cesar
dc.contributor.author Vasilopoulos, Yiannis
dc.contributor.author Caliz, Rafael
dc.contributor.author Ferrer, Miguel Ángel
dc.contributor.author Joven, Beatriz
dc.contributor.author Carreira, Patricia
dc.contributor.author Balsa, Alejandro
dc.contributor.author Pascual-Salcedo, Dora
dc.contributor.author Blanco, Francisco J.
dc.contributor.author Moreno-Ramos, Manuel J.
dc.contributor.author Manrique-Arija, Sara
dc.contributor.author Carmen Ordoñez, María del
dc.contributor.author Alegre-Sancho, Juan Jose
dc.contributor.author Narvaez, Javier
dc.contributor.author Navarro-Sarabia, Federico
dc.contributor.author Moreira, Virginia
dc.contributor.author Valor, Lara
dc.contributor.author Garcia-Portales, Rosa
dc.contributor.author Marquez, Ana
dc.contributor.author Gomez-Reino, Juan J.
dc.contributor.author Martin, Javier
dc.contributor.author Gonzalez, Antonio
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.date.accessioned 2019-04-26T10:12:30Z
dc.date.available 2019-04-26T10:12:30Z
dc.date.issued 2019-02-28
dc.identifier.citation PLoS ONE 14.2 (2019): e0213073 en_US
dc.identifier.issn 1932-6203 es_ES
dc.identifier.uri http://hdl.handle.net/10486/687360
dc.description.abstract 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 nonredundant 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 metaanalysis 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 en_US
dc.description.sponsorship This work was supported by the Instituto de Salud Carlos III (ISCIII, Spain) through grants PI14/01651, PI17/01606 and RD16/0012/0014 to AG and PI12/01909 to JJG-R. These grants are partially financed by the European Regional Development Fund of the EU (FEDER) en_US
dc.format.extent 14 págs. es_ES
dc.format.mimetype application/pdf es_ES
dc.language.iso eng es_ES
dc.publisher Public Library of Science en_US
dc.relation.ispartof PLoS ONE en_US
dc.rights © 2019 Ferreiro-Iglesias et al. es_ES
dc.subject.other arthritis RA en_US
dc.subject.other arthritis, Reumatoid en_US
dc.subject.other tumor Necrosis Factor-alpha en_US
dc.title Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept en_US
dc.type article en_US
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion https://doi.org/10.1371/journal. pone.0213073 es_ES
dc.identifier.doi 10.1371/journal.pone.0213073 es_ES
dc.identifier.publicationfirstpage e0213073-1 es_ES
dc.identifier.publicationissue 2 es_ES
dc.identifier.publicationlastpage e0213073-14 es_ES
dc.identifier.publicationvolume 14 es_ES
dc.relation.projectID Gobierno de España. PI14/01651 es_ES
dc.relation.projectID Gobierno de España. PI17/01606 es_ES
dc.relation.projectID Gobierno de España. RD16/0012/0014 es_ES
dc.relation.projectID Gobierno de España. PI12/01909 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en_US
dc.authorUAM Balsa Criado, Alejandro (259517)

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