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BioMed Research International
Volume 2014, Article ID 368681, 11 pages
Research Article

Prediction of Methotrexate Clinical Response in Portuguese Rheumatoid Arthritis Patients: Implication of MTHFR rs1801133 and ATIC rs4673993 Polymorphisms

1CESPU, 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
2Molecular Oncology Group CI, Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
3Abel Salazar Institute for the Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
4Faculty of Medicine of University of Porto (FMUP), Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
5Rheumatology Department, São João Hospital Center, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
6Virology Service, Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
7Research Department-Portuguese League Against Cancer (LPCC-NRNorte), Estrada Interior da Circunvalação 6657, 4200-177 Porto, Portugal

Received 28 February 2014; Revised 22 April 2014; Accepted 22 April 2014; Published 21 May 2014

Academic Editor: Miguel A. González-Gay

Copyright © 2014 Aurea Lima et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Objective. 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 (MTHFR) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase (ATIC) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese RA patients. Methods. Study included 233 RA patients treated with MTX for at least six months. MTHFR C677T and ATIC T675C polymorphisms were genotyped and clinicopathological variables were collected. Statistical analyses were performed and binary logistic regression method adjusted to possible confounding variables. Results. Multivariate analyses demonstrated that MTHFR 677TT (OR = 4.63; ) and ATIC 675T carriers (OR = 5.16; ) were associated with over 4-fold increased risk for nonresponse. For clinicopathological variables, noncurrent smokers (OR = 7.98; ), patients positive to anti-cyclic citrullinated peptide (OR = 3.53; ) and antinuclear antibodies (OR = 2.28; ), with higher health assessment questionnaire score (OR = 2.42; ), and nonsteroidal anti-inflammatory drug users (OR = 2.77; ) were also associated with nonresponse. Contrarily, subcutaneous administration route (OR = 0.11; ) was associated with response. Conclusion. Our study suggests that MTHFR C677T and ATIC 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.