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

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Lima, A (Author) Other; Monteiro, J (Author) Other; Bernardes, M (Author) Other; Sousa, H (Author) Other; Azevedo, R (Author) Other; Seabra, V (Author) Other; Rui Medeiros (Author) ICBAS

Journal

Title: BioMed Research International

Vol. 2014

Pages: 1-11

ISSN: 2314-6133

Publisher: Hindawi

Indexing

ISI Web of Knowledge - 34 Citations

Scopus - 37 Citations

Other information

Authenticus ID: P-009-H92

DOI: 10.1155/2014/368681

Abstract (EN): 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;P = 0.013) and ATIC 675T carriers (OR = 5.16;P = 0.013) were associated with over 4-fold increased risk for nonresponse. For clinicopathological variables, noncurrent smokers (OR = 7.98;P = 0.001), patients positive to anti-cyclic citrullinated peptide (OR = 3.53;P = 0.004) and antinuclear antibodies (OR = 2.28;P = 0.045), with higher health assessment questionnaire score (OR = 2.42;P = 0.007), and nonsteroidal anti-inflammatory drug users (OR = 2.77;P = 0.018) were also associated with nonresponse. Contrarily, subcutaneous administration route (OR = 0.11;P < 0.001) 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11