Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/147782
Title: Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept
Author: Ferreiro Iglesias, Aída
Montes, Ariana
Perez-Pampin, Eva
Cañete Crespillo, Juan D.
Raya, Enrique
Magro Checa, Cesar
Vasilopoulos, Yiannis
Caliz, Rafael
Ferrer, Miguel Angel
Joven, Beatriz
Carreira, Patricia
Balsa, Alejandro
Pascual-Salcedo, Dora
Blanco, Francisco J.
Moreno-Ramos, Manuel J.
Manrique Arija, Sara
Ordóñez, María del Carmen
Alegre Sancho, Juan Jose
Narváez García, Francisco Javier
Navarro Sarabia, Federico
Moreira, Virginia
Valor, Lara
Garcia Portales, Rosa
Márquez, Ana
Gomez Reino, Juan J.
Martín, Javier
Gonzalez, Antonio
Keywords: Artritis reumatoide
Genomes
Marcadors bioquímics
Rheumatoid arthritis
Genomes
Biochemical markers
Issue Date: 28-Feb-2019
Publisher: Public Library of Science (PLoS)
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 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
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0213073
It is part of: PLoS One, 2019, vol. 14, num. 2, p. e0213073
URI: http://hdl.handle.net/2445/147782
Related resource: https://doi.org/10.1371/journal.pone.0213073
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Ciències Clíniques)

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