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oai:repisalud.isciii.es:20.500.12105/178232024-02-10T20:00:50Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16961col_20.500.12105_16963col_20.500.12105_16966col_20.500.12105_16985
Repisalud author Ferreiro-Iglesias, Aida author Montes, Ariana author Perez-Pampin, Eva author Cañete, Juan D author Raya, Enrique author Magro-Checa, Cesar author Vasilopoulos, Yiannis author Caliz, Rafael author Ferrer, Miguel Angel author Joven, Beatriz author Carreira, Patricia author Balsa, Alejandro author Pascual-Salcedo, Dora author Blanco, Francisco J author Moreno-Ramos, Manuel J author Manrique-Arija, Sara author Ordoñez, María Del Carmen author Alegre-Sancho, Juan Jose author Narvaez, Javier author Navarro-Sarabia, Federico author Moreira, Virginia author Valor, Lara author Garcia-Portales, Rosa author Marquez, Ana author Gomez-Reino, Juan J author Martin, Javier author Gonzalez, Antonio 2024-02-10T20:00:50Z 2024-02-10T20:00:50Z 2019-02-28 http://hdl.handle.net/10668/13641 http://hdl.handle.net/20.500.12105/17823 30818333 10.1371/journal.pone.0213073 1932-6203 PloS one 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. eng Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept. research article