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Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis

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 larg...

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Published in:Scientific reports 2018-05, Vol.8 (1), p.7342-8, Article 7342
Main Authors: López-Rodríguez, Rosario, Ferreiro-Iglesias, Aida, Lima, Aurea, Bernardes, Miguel, Pawlik, Andrzej, Paradowska-Gorycka, Agnieszka, Świerkot, Jerzy, Slezak, Ryszard, Dolžan, Vita, González-Álvaro, Isidoro, Narváez, Javier, Cáliz, Rafael, Pérez-Pampín, Eva, Mera-Varela, Antonio, Vidal-Bralo, Laura, Acuña Ochoa, José Gorgonio, Conde, Carmen, Gómez-Reino, Juan J., González, Antonio
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cited_by cdi_FETCH-LOGICAL-c588t-8270f6f18aabf6a4224a0939b41bdc7a5da732a847de4a674843ed2261185a8b3
cites cdi_FETCH-LOGICAL-c588t-8270f6f18aabf6a4224a0939b41bdc7a5da732a847de4a674843ed2261185a8b3
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container_title Scientific reports
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creator López-Rodríguez, Rosario
Ferreiro-Iglesias, Aida
Lima, Aurea
Bernardes, Miguel
Pawlik, Andrzej
Paradowska-Gorycka, Agnieszka
Świerkot, Jerzy
Slezak, Ryszard
Dolžan, Vita
González-Álvaro, Isidoro
Narváez, Javier
Cáliz, Rafael
Pérez-Pampín, Eva
Mera-Varela, Antonio
Vidal-Bralo, Laura
Acuña Ochoa, José Gorgonio
Conde, Carmen
Gómez-Reino, Juan J.
González, Antonio
description 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.
doi_str_mv 10.1038/s41598-018-25634-y
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subjects 45
45/22
45/77
692/4017
692/4023/1670/498
692/53/2423
692/699/1670/427/1304
Alleles
Autoimmune diseases
Biomarkers
Corticosteroids
Folic acid
Humanities and Social Sciences
Methotrexate
multidisciplinary
Patients
Rheumatoid arthritis
Science
Science (multidisciplinary)
Single-nucleotide polymorphism
Smoking
title Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis
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