Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients.

BACKGROUND: Methotrexate, a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis. However, high interindividual differences in drug response are present among RA patients.

RESEARCH DESIGN AND METHODS: In a group of 234 RA patients treated with MTX we investigated whether rs1650697 polymorphism in DHFR gene may have impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for MTX therapy estimation and all adverse drug events were recorded. Patients were genotyped for selected polymorphism by real-time PCR method.

RESULTS: According to the EULAR criteria after 6 months of MTX therapy 196 patients (83.8 %) were classified as responders, (25 (10.7 %) were good and 171 (73.1 %) were moderate) and 38 patients (16.2 %) as non-responders. ADEs were observed in 55 patients (23.5 %).

CONCLUSIONS: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminaze levels (p=0.05). Furthermore, among patients who also received low-dose corticosteroids we have found a lower rDAS values in patients with CC genotype (p=0.039).