Márquez, AnaFerreiro-Iglesias, AidaDávila-Fajardo, Cristina LMontes, ArianaPascual-Salcedo, DoraPerez-Pampin, EvaMoreno-Ramos, Manuel JGarcía-Portales, RosaNavarro, FedericoMoreira, VirginiaMagro, CésarCaliz, RafaelFerrer, Miguel AngelAlegre-Sancho, Juan JoséJoven, BeatrizCarreira, PatriciaBalsa, AlejandroVasilopoulos, YiannisSarafidou, TheologiaCabeza-Barrera, JoséNarvaez, JavierRaya, EnriqueCañete, Juan DFernández-Nebro, AntonioOrdóñez, María del Carmende la Serna, Arturo RMagallares, BertaGomez-Reino, Juan JGonzález, AntonioMartín, Javier2016-08-082016-08-082014-03-11Márquez A, Ferreiro-Iglesias A, Dávila-Fajardo CL, Montes A, Pascual-Salcedo D, Perez-Pampin E, et al. Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis. Arthritis Res. Ther. 2014; 16(2):R661478-6354http://hdl.handle.net/10668/2316Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't;INTRODUCTION In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. METHODS The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. RESULTS None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. CONCLUSION Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.enAntirreumáticosArtritis reumatoideEstudio de asociación del genoma completoGenotipoPolimorfismo de nucleótido simpleResultado del tratamientoFactor de necrosis tumoral alfaMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antirheumatic AgentsMedical Subject Headings::Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Rheumatic Diseases::Arthritis, RheumatoidMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies::Genome-Wide Association StudyMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Tumor Necrosis Factors::Tumor Necrosis Factor-alphaMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Agedresearch article24612463open access10.1186/ar45041478-6362PMC4060376