Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis
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...
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2018
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oai:doaj.org-article:2feae63c8b2a4e138135868ba1a187e32021-12-02T11:40:16ZReplication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis10.1038/s41598-018-25634-y2045-2322https://doaj.org/article/2feae63c8b2a4e138135868ba1a187e32018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25634-yhttps://doaj.org/toc/2045-2322Abstract 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.Rosario López-RodríguezAida Ferreiro-IglesiasAurea LimaMiguel BernardesAndrzej PawlikAgnieszka Paradowska-GoryckaJerzy ŚwierkotRyszard SlezakVita DolžanIsidoro González-ÁlvaroJavier NarváezRafael CálizEva Pérez-PampínAntonio Mera-VarelaLaura Vidal-BraloJosé Gorgonio Acuña OchoaCarmen CondeJuan J. Gómez-ReinoAntonio GonzálezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018) |
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Medicine R Science Q Rosario López-Rodríguez Aida Ferreiro-Iglesias Aurea Lima Miguel Bernardes Andrzej Pawlik Agnieszka Paradowska-Gorycka Jerzy Świerkot Ryszard Slezak Vita Dolžan Isidoro González-Álvaro Javier Narváez Rafael Cáliz Eva Pérez-Pampín Antonio Mera-Varela Laura Vidal-Bralo José Gorgonio Acuña Ochoa Carmen Conde Juan J. Gómez-Reino Antonio González Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis |
| description |
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. |
| format |
article |
| author |
Rosario López-Rodríguez Aida Ferreiro-Iglesias Aurea Lima Miguel Bernardes Andrzej Pawlik Agnieszka Paradowska-Gorycka Jerzy Świerkot Ryszard Slezak Vita Dolžan Isidoro González-Álvaro Javier Narváez Rafael Cáliz Eva Pérez-Pampín Antonio Mera-Varela Laura Vidal-Bralo José Gorgonio Acuña Ochoa Carmen Conde Juan J. Gómez-Reino Antonio González |
| author_facet |
Rosario López-Rodríguez Aida Ferreiro-Iglesias Aurea Lima Miguel Bernardes Andrzej Pawlik Agnieszka Paradowska-Gorycka Jerzy Świerkot Ryszard Slezak Vita Dolžan Isidoro González-Álvaro Javier Narváez Rafael Cáliz Eva Pérez-Pampín Antonio Mera-Varela Laura Vidal-Bralo José Gorgonio Acuña Ochoa Carmen Conde Juan J. Gómez-Reino Antonio González |
| author_sort |
Rosario López-Rodríguez |
| title |
Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis |
| title_short |
Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis |
| title_full |
Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis |
| title_fullStr |
Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis |
| title_full_unstemmed |
Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis |
| title_sort |
replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/2feae63c8b2a4e138135868ba1a187e3 |
| work_keys_str_mv |
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1718395633596891136 |