{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T10:55:27Z","timestamp":1774868127777,"version":"3.50.1"},"reference-count":102,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T00:00:00Z","timestamp":1434412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) treatment. Single nucleotide polymorphisms (SNPs) could be used as predictors of patients\u2019 therapeutic outcome variability. Therefore, this study aims to evaluate the influence of SNPs in genes encoding for MTX membrane transport proteins in order to predict clinical response to MTX. Methods: Clinicopathological data from 233 RA patients treated with MTX were collected, clinical response defined, and patients genotyped for 23 SNPs. Genotype and haplotype analyses were performed using multivariate methods and a genetic risk index (GRI) for non-response was created. Results: Increased risk for non-response was associated to SLC22A11 rs11231809 T carriers; ABCC1 rs246240 G carriers; ABCC1 rs3784864 G carriers; CGG haplotype for ABCC1 rs35592, rs2074087 and rs3784864; and CGG haplotype for ABCC1 rs35592, rs246240 and rs3784864. GRI demonstrated that patients with Index 3 were 16-fold more likely to be non-responders than those with Index 1. Conclusions: This study revealed that SLC22A11 and ABCC1 may be important to identify those patients who will not benefit from MTX treatment, highlighting the relevance in translating these results to clinical practice. However, further validation by independent studies is needed to develop the field of personalized medicine to predict clinical response to MTX treatment.<\/jats:p>","DOI":"10.3390\/ijms160613760","type":"journal-article","created":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T10:28:09Z","timestamp":1434450489000},"page":"13760-13780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Pharmacogenomics of Methotrexate Membrane Transport Pathway: Can Clinical Response to Methotrexate in Rheumatoid Arthritis Be Predicted?"],"prefix":"10.3390","volume":"16","author":[{"given":"Aurea","family":"Lima","sequence":"first","affiliation":[{"name":"Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio (CESPU), Instituto de Investiga\u00e7\u00e3o e Forma\u00e7\u00e3o Avan\u00e7ada em Ci\u00eancias e Tecnologias da Sa\u00fade (IINFACTS), 4585-116 Gandra PRD, Portugal"},{"name":"Grupo de Oncologia Molecular & Patologia Viral\u2014Centro de Investiga\u00e7\u00e3o do Instituto Portugu\u00eas de Oncologia do Porto (CI-IPOP), 4200-072 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar da Universidade do Porto (ICBAS-UP), 4050-313 Porto, Portugal"}]},{"given":"Miguel","family":"Bernardes","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universidade do Porto (FMUP), 4200-319 Porto, Portugal"},{"name":"Departamento de Reumatologia do Centro Hospitalar de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Rita","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar da Universidade do Porto (ICBAS-UP), 4050-313 Porto, Portugal"},{"name":"Grupo de Patologia & Terap\u00eautica Experimental do Centro de Investiga\u00e7\u00e3o do Instituto Portugu\u00eas de Oncologia do Porto (CI-IPOP), 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Grupo de Oncologia Molecular & Patologia Viral\u2014Centro de Investiga\u00e7\u00e3o do Instituto Portugu\u00eas de Oncologia do Porto (CI-IPOP), 4200-072 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar da Universidade do Porto (ICBAS-UP), 4050-313 Porto, Portugal"}]},{"given":"V\u00edtor","family":"Seabra","sequence":"additional","affiliation":[{"name":"Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio (CESPU), Instituto de Investiga\u00e7\u00e3o e Forma\u00e7\u00e3o Avan\u00e7ada em Ci\u00eancias e Tecnologias da Sa\u00fade (IINFACTS), 4585-116 Gandra PRD, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,16]]},"reference":[{"key":"ref_1","first-page":"E427","article-title":"Painful rheumatoid arthritis","volume":"14","author":"Smith","year":"2011","journal-title":"Pain Phys."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/med.2610080106","article-title":"The chemistry of methotrexate and its analogues","volume":"8","author":"Rahman","year":"1988","journal-title":"Med. 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