Factors associated with rs1801394 of the methionine synthase reductase gene polymorphism in patients with rheumatoid arthritis

Clinical response to methotrexate (MT) therapy in rheumatoid arthritis (RA) can be predicted on the basis of some single nucleotide polymorphisms (SNPs) of genes, involved in folate metabolism. One of these SNPs is the rs1801394 (A66G) polymorphism of the methionine synthase reductase gene (MTRR). We investigated the association of this polymorphism with the clinical characteristics of RA patients after 6 months of MT therapy. Studies of the relationship between the response to MT therapy and the rs1801394 polymorphism have not been carried out in Russia previously.

Objective: to study the possible association of the rs1801394 polymorphism with the clinical characteristics of patients with RA after 6 months of MT therapy.

Patients and methods. The study included 60 patients with RA who met the ACR / EULAR criteria (2010) and received≥20 mg MT per week continuously. Based on the EULAR criteria, patients were divided into two groups: group 1 (n=30) with a good (DAS28>1.2) and group 2 (n=30) with an unsatisfactory (DAS28 <1.2) response to MT therapy. Genotyping of the rs1801394 polymorphism was performed by allelic discrimination using real-time polymerase chain reaction.

Results and discussion. The frequency distribution of the A66G polymorphism genotypes in both groups was similar, however, in the 2nd group with an unsatisfactory response, there was a tendency towards a higher frequency of the mutant GG genotype (p=0.067). An association of the A66G polymorphism with gender and disease duration was found. In group 1, the AG genotype was more often detected in men than in women (p=0.017). In group 2, the AG genotype was also more common in men (p=0.075). In addition, in this group, carriers of the G allele (genotypes AG and GG) had a longer duration of the disease than carriers of the AA genotype (p=0.003 and p=0.005, respectively).

Conclusion. In the present study, the relationship of the studied polymorphism rs1801394 of the MTRR gene with gender and duration of RA disease was established.

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