The C677T polymorphism in the methylentetrahydrofolate reductase gene is associated with methotrexate treatment outcome in the East Bohemian region rheumatoid arthritis population


Authors: T. Soukup 1;  M. Doseděl 2;  P. Pávek 3;  J. Nekvindová 4;  T. Veleta 5;  A. Kuběna 2;  M. Tošovský 1;  J. Vlček 2;  P. Bradna 1
Authors‘ workplace: Univerzita Karlova v Praze, Lékařská fakulta a Fakultní nemocnice v Hradci Králové, II. interní gastroenterologická klinika 1;  Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové, Katedra sociální a klinické farmacie 2;  Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové, katedra farmakologie a toxikologie 3;  Univerzita Karlova v Praze, Lékařská fakulta a Fakultní nemocnice v Hradci Králové, Ústav klinické biochemie a diagnostiky 4;  Fakultní nemocnice Hradec Králové, Oddělení urgentní medicíny 5
Published in: Čes. Revmatol., 23, 2015, No. 1, p. 4-12.
Category: Original article

Overview

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 (∆DAS 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 ∆DAS 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.

Key words:
Rheumatoid arthritis, methotrexate, methylentetrahydrofolate reductase, pharmacogenetics, personalized medicine


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Labels
Dermatology & STDs Paediatric rheumatology Rheumatology
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