{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T09:06:13Z","timestamp":1766653573853},"reference-count":60,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3ao para a Ci\u00eancia e Tecnologia","award":["SFRH\/BD\/64441\/2009"],"award-info":[{"award-number":["SFRH\/BD\/64441\/2009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:p><jats:italic>Objective.<\/jats:italic>Methotrexate (MTX), the most used drug in rheumatoid arthritis (RA) treatment, showing variability in clinical response, is often associated with genetic polymorphisms. This study aimed to elucidate the role of methylenetetrahydrofolate reductase (<jats:italic>MTHFR<\/jats:italic>) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase (<jats:italic>ATIC<\/jats:italic>) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese RA patients.<jats:italic>Methods.<\/jats:italic>Study included 233 RA patients treated with MTX for at least six months.<jats:italic>MTHFR<\/jats:italic>C677T and<jats:italic>ATIC<\/jats:italic>T675C polymorphisms were genotyped and clinicopathological variables were collected. Statistical analyses were performed and binary logistic regression method adjusted to possible confounding variables.<jats:italic>Results.<\/jats:italic>Multivariate analyses demonstrated that<jats:italic>MTHFR<\/jats:italic>677TT (OR = 4.63;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.013<\/mml:mn><\/mml:math>) and<jats:italic>ATIC<\/jats:italic>675T carriers (OR = 5.16;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.013<\/mml:mn><\/mml:math>) were associated with over 4-fold increased risk for nonresponse. For clinicopathological variables, noncurrent smokers (OR = 7.98;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:math>), patients positive to anti-cyclic citrullinated peptide (OR = 3.53;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.004<\/mml:mn><\/mml:math>) and antinuclear antibodies (OR = 2.28;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.045<\/mml:mn><\/mml:math>), with higher health assessment questionnaire score (OR = 2.42;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.007<\/mml:mn><\/mml:math>), and nonsteroidal anti-inflammatory drug users (OR = 2.77;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.018<\/mml:mn><\/mml:math>) were also associated with nonresponse. Contrarily, subcutaneous administration route (OR = 0.11;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\"><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:math>) was associated with response.<jats:italic>Conclusion.<\/jats:italic>Our study suggests that<jats:italic>MTHFR<\/jats:italic>C677T and<jats:italic>ATIC<\/jats:italic>T675C genotyping combined with clinicopathological data may help to identify patients whom will not benefit from MTX treatment and, therefore, assist clinicians in personalizing RA treatment.<\/jats:p>","DOI":"10.1155\/2014\/368681","type":"journal-article","created":{"date-parts":[[2014,5,21]],"date-time":"2014-05-21T21:08:29Z","timestamp":1400706509000},"page":"1-11","source":"Crossref","is-referenced-by-count":25,"title":["Prediction of Methotrexate Clinical Response in Portuguese Rheumatoid Arthritis Patients: Implication of<i>MTHFR<\/i>rs1801133 and<i>ATIC<\/i>rs4673993 Polymorphisms"],"prefix":"10.1155","volume":"2014","author":[{"given":"Aurea","family":"Lima","sequence":"first","affiliation":[{"name":"CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Pharmaceutical Sciences, Higher Institute of Health Sciences (ISCS-N), Rua Central de Gandra 1317, 4585-116 Gandra PRD, Portugal"},{"name":"Molecular Oncology Group CI, Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Abel Salazar Institute for the Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Joaquim","family":"Monteiro","sequence":"additional","affiliation":[{"name":"CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Pharmaceutical Sciences, Higher Institute of Health Sciences (ISCS-N), Rua Central de Gandra 1317, 4585-116 Gandra PRD, Portugal"}]},{"given":"Miguel","family":"Bernardes","sequence":"additional","affiliation":[{"name":"Faculty of Medicine of University of Porto (FMUP), Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Rheumatology Department, S\u00e3o Jo\u00e3o Hospital Center, Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Hugo","family":"Sousa","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group CI, Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine of University of Porto (FMUP), Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Virology Service, Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Rita","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group CI, Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine of University of Porto (FMUP), Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Vitor","family":"Seabra","sequence":"additional","affiliation":[{"name":"CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Pharmaceutical Sciences, Higher Institute of Health Sciences (ISCS-N), Rua Central de Gandra 1317, 4585-116 Gandra PRD, Portugal"}]},{"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group CI, Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Abel Salazar Institute for the Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Virology Service, Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Research Department-Portuguese League Against Cancer (LPCC-NRNorte), 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