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2019-02-28

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cc-by (c) Ferreiro Iglesias, Aída et al., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/147782

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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https://doi.org/10.1371/journal.pone.0213073

Resum

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

Matèries

Artritis reumatoide, Genomes, Marcadors bioquímics

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Rheumatoid arthritis, Genomes, Biochemical markers

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Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

FERREIRO IGLESIAS, Aida, MONTES, Ariana, PÉREZ 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 josé, NARVÁEZ GARCÍA, Francisco javier, NAVARRO SARABIA, Federico, MOREIRA, Virginia, VALOR, Lara, GARCÍA PORTALES, Rosa, MÁRQUEZ, Ana, GOMEZ REINO, Juan j., MARTÍN, Javier, GONZALEZ, Antonio. 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. Vol. 14, núm. 2, pàgs. e0213073. [consulta: 20 de gener de 2026]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/147782]

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