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, Aida; Montes, Ariana; Perez-Pampin, Eva; Cañete, Juan D.; Raya, Enrique; Magro-Checa, Cesar; Vasilopoulos, Yiannis; Caliz, Rafael; Ferrer, Miguel Ángel; Joven, Beatriz; Carreira, Patricia; Balsa Criado, Alejandro; Pascual-Salcedo, Dora; Blanco, Francisco J.; Moreno-Ramos, Manuel J.; Manrique-Arija, Sara; Carmen Ordoñez, María del; Alegre-Sancho, Juan Jose; Narvaez, Javier; Navarro-Sarabia, Federico; Moreira, Virginia; Valor, Lara; Garcia-Portales, Rosa; Marquez, Ana; Gomez-Reino, Juan J.; Martin, Javier; Gonzalez, AntonioEntity
UAM. Departamento de MedicinaPublisher
Public Library of ScienceDate
2019-02-28Citation
10.1371/journal.pone.0213073
PLoS ONE 14.2 (2019): e0213073
ISSN
1932-6203DOI
10.1371/journal.pone.0213073Funded by
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)Project
Gobierno de España. PI14/01651; Gobierno de España. PI17/01606; Gobierno de España. RD16/0012/0014; Gobierno de España. PI12/01909Editor's Version
https://doi.org/10.1371/journal. pone.0213073Subjects
arthritis RA; arthritis, Reumatoid; tumor Necrosis Factor-alpha; MedicinaRights
© 2019 Ferreiro-Iglesias et al.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
Files in this item
Google Scholar:Ferreiro-Iglesias, Aida
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Montes, Ariana
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Perez-Pampin, Eva
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Cañete, Juan D.
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Raya, Enrique
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Magro-Checa, Cesar
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Vasilopoulos, Yiannis
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Caliz, Rafael
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Ferrer, Miguel Ángel
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Joven, Beatriz
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Carreira, Patricia
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Balsa Criado, Alejandro
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Pascual-Salcedo, Dora
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Blanco, Francisco J.
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Moreno-Ramos, Manuel J.
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Manrique-Arija, Sara
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Carmen Ordoñez, María del
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Alegre-Sancho, Juan Jose
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Narvaez, Javier
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Navarro-Sarabia, Federico
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Moreira, Virginia
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Valor, Lara
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Garcia-Portales, Rosa
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Marquez, Ana
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Gomez-Reino, Juan J.
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Martin, Javier
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Gonzalez, Antonio
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