Association of 63/91 length polymorphism in the DHFR gene major promoter with toxicity of methotrexate in patients with rheumatoid arthritis.

Aim: Our aim was to explore the influence of 9-bp insertion/deletion and variable number of 9 bp elements (63/91) length polymorphism in noncoding interfering RNA and major promoter of DHFR gene on methotrexate (MTX) efficacy and toxicity in patients with rheumatoid arthritis (RA).

Patients & Methods: Response to the MTX therapy and adverse effects were estimated in 243 RA patients genotyped for the selected polymorphism.

Results: The presence of allele 1 of analyzed polymorphism had significant protective effect against MTX toxicity (odds ratio: 0.37 [95% CI: 0.19-0.70]; p = 0.002). Results remained significant in multiple logistic regression analysis with the inclusion of disease and treatment features in the model (p = 0.03).

Conclusion: Polymorphism 63/91 in DHFR gene promoter can modulate the onset of MTX-related adverse effects in RA patients.