Association of RFC-1 and MDR1 transporter gene polymorphisms with therapeutic response to methotrexate in rheumatoid arthritis patients

Rheumatoid arthritis (RA) is “an immunoin ammatory (autoimmune) rheumatic disease characterized by severe progressive joint and internal organ damage, the development of which is determined by a complex in-teraction of environmental factors and genetic predisposition, leading to global disturbances in the humoral and cellular immunity system. Methotrexate (MT) leads the therapy of RA. To date, anti-in ammatory MT therapy in RA patients has been carried out empirically with observational tactics regarding e cacy. At the same time, in a number of individuals the goals of treatment aimed at slowing the progression of the disease may not be achieved. This makes the search for various prognostic markers of MT e cacy relevant. According to recent literature data, the attention of researchers is focused on single nucleotide polymorphisms (SNP - single nucleotide polymorphism) of a number of folate cycle genes that regulate the mechanism of MT action, including its intra- and extracellular transport processes. Objective: To evaluate the prognostic role of single-nucleotide polymorphisms of RFC-1 80G>A and MDR1 C3435T transporter genes in the formation of therapeutic response to MT in RA patients.Materials and methods. The study group consisted of 85 patients with a reliable diagnosis of RA, who were initi-ated on anti-in ammatory therapy with MT at a dose of 10 to 17.5 mg/week. E cacy was monitored after 6 months of treatment by the dynamics of the DAS28. During follow-up, “responders” and “nonresponders” to MT were identi ed. Ampli cation of RFC-1 and MDR1 transporter gene polymorphisms was performed by real-time polymerase chain reaction. Results. In the groups of “responders” and “nonresponders” we found trends towards di erences in the frequency of RFC-1 80G>A and MDR1 C3435T alleles and genotypes and signi cant di erences in the frequency of certain genotypic combinations. Thus, the RFC-1 80AG+MDR1 3435CT combination prevailed in patients with MT e cacy (OR=0.2; 95 % CI 0.05 to 0.76; p=0.019), and the RFC-1 80AG+MDR1 3435T combination prevailed in treatment-resistant patients (OR=4.7; 95 % CI 1.2 to 18.7; p=0.027). Conclusion. Transporter polymorphisms RFC-1 80G>A and MDR1 C3435T may play a role in the therapeutic response to MTs, but intergenic interactions rather than their isolated mutations in uence this.