Abstract

About 70 genetic studies have already addressed the need of biomarkers to predict the response of patients with rheumatoid arthritis (RA) to methotrexate (MTX) treatment. However, no genetic biomarker has yet been sufficiently validated. Here, we aimed to replicate a selection of 25 SNPs in the largest collection of patients up to date, which consisted of 915 patients treated with MTX. The change in disease activity (measured as ΔDAS28) from baseline was considered the primary outcome. In addition, response according to widely used criteria (EULAR) was taken as secondary outcome. We considered consistency between outcomes, P values accounting for the number of SNPs, and independence from potential confounders for interpretation of the results. Only the rs1801394 SNP in MTRR fulfilled the high association standards. Its minor allele was associated with less improvement than the major allele according to ΔDAS28 (p = 0.0016), and EULAR response (p = 0.004), with independence of sex, age, baseline DAS28, smoking, seropositivity, concomitant corticosteroid use or previous treatments. In addition, previous evidence suggests the association of this SNP with response to MTX in another autoimmune disease, juvenile idiopathic arthritis, and with high intracellular folate levels, which could contribute to poor response.

Details

Title
Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis
Author
López-Rodríguez, Rosario 1 ; Ferreiro-Iglesias, Aida 1 ; Lima, Aurea 2 ; Bernardes, Miguel 3 ; Pawlik, Andrzej 4 ; Paradowska-Gorycka, Agnieszka 5 ; Świerkot, Jerzy 6 ; Slezak, Ryszard 7 ; Dolžan, Vita 8 ; González-Álvaro, Isidoro 9 ; Narváez, Javier 10 ; Cáliz, Rafael 11 ; Pérez-Pampín, Eva 1 ; Mera-Varela, Antonio 1 ; Vidal-Bralo, Laura 1 ; José Gorgonio Acuña Ochoa 1 ; Conde, Carmen 1 ; Gómez-Reino, Juan J 1 ; González, Antonio 1   VIAFID ORCID Logo 

1  Experimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigación Sanitaria - Hospital Clínico Universitario de Santiago, Travesia Choupana sn, Santiago de Compostela, Spain 
2  CESPU, Institute of Research & Advanced Training in Health Sciences & Technologies, Department of Pharmaceutical Sciences, Gandra, PRD, Portugal 
3  Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, Porto, Portugal; Rheumatology Department of São João Hospital Center, Porto, Portugal 
4  Department of Physiology, Pomeranian Medical University Szczecin, Szczecin, Poland 
5  Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, Warsaw, Poland 
6  Department of Rheumatology, Wroclaw Medical University, Wroclaw, Poland 
7  Department of Genetics, Wroclaw Medical University, Wroclaw, Poland 
8  Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 
9  Rheumatology Department, Instituto de Investigacion del Hospital de La Princesa (IIS-IP), Madrid, Spain 
10  Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, Carrer de la Feixa Llarga, s/n, Barcelona, Spain 
11  Rheumatology Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain 
Pages
1-8
Publication year
2018
Publication date
May 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-25634-y
ProQuest document ID
2036770798
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.