The C677T Polymorphism in the Methylentetrahydrofolate Reductase Gene is Associated with Methotrexate Treatment Outcome in the East Bohemian Region Rheumatoid Arthritis Population
Abstract
Methotrexate (MTX) is one of the essential medicines used in the treatment of rheumatoid arthritis (RA). The efficacy of treatment of rheumatoid arthritis with MTX is between 46 % and 65 % (as assessed by ACR 20).
Pharmacogenetics deals with genetic predisposition of the patient to respond to the treatment. The aim of the study was to determine whether single nucleotide polymorphism (SNP) C677T (rs1801133) of the MTHFR gene are predictive of peroral MTX efficacy or are associated with lower change of DAS28 (DeltaDAS 28) after a 6-month MTX treatment in RA adult patient cohort of the East Bohemian population.
The 120 patients were enrolled in the study, all of whom fulfilled the American College of Rheumatology (ACR) 1987 RA criteria, and currently or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a combination with DMARDs (n = 55). Genotyping was performed using qPCR allelic discrimination.
We did not found any association of C677T SNP on MTX treatment inefficacy in dominant model CC versus (CT+TT). However, when DeltaDAS 28 was used as a measure of MTX treatment efficacy, MTHFR 677CT genotype was significantly associates with less favourable response to MTX (P = 0.01) in case of MTX monotherapy.
Our data thus shows that C677T SNP might be associated with theless favourable response to low dose MTX treatment.