POSSIBILITIES OF USING THE GENOTYPING OF CYTOKINES WITH INFLAMMATION-REGULATORY ACTIVITY AS BIOLOGICAL MARKERS FOR PREDICTION OF THE EFFICIENCY OF THERAPY FOR RHEUMATOID ARTHRITIS

Objective. To reveal the genetic markers that may predict the efficiency of therapy for rheumatoid arthritis (RA).
Subjects and methods. The study enrolled 104 patients (93 women and 11 men) (mean age 53.38+13.55 years). The duration of RA averaged 9.18+8.97 years. The patients were treated with basic anti-inflammatory drugs (BAIDs): 69.23% took methotrexate (MT), 10-17.5 mg/week; 30.77% received sulfasalazine, 2 g/day. Therapeutic effectiveness was evaluated using the European League Against Rheumatism (EULAR) criteria following 24 weeks. Clinical and laboratory parameters were similar in MT- and sulfasalazine-treated patients. The patients groups showing the varying efficacy of BAIDs were analyzed from the similar cutoffs of polymorphisms of the same cytokine genes.
Results. The study indicated that some patients with certain combinations of allelic variants of promoter regions of cytokine genes had no benefits from BAID therapy. There was a preponderance of alleles in the genes associated with the high production of IL-1, the low generation of IL-6, and the low elaboration of cytokines with anti-inflammatory activity in the group of patients unresponsive to the basic therapy. The patients having many benefits from the performed treatment showed a predominance of alleles associated with the high production of IL-6 and the low generation of IL-1, with a tendency towards an increase in the frequency of alleles in the IL-1 and IL-10 genes that ensured a high elaboration of anti-inflammatory cytokines.
Conclusion. The findings suggest that the effect of basic anti-rheumatic therapy with methotrexate or sulfasalazine largely depends on the cytokine genotype of a patient. Analysis of appropriate factors is likely to be used in rheumatological care.

rheumatoid arthritis, basic anti-inflammatory drugs, genetic markers, proinflammatory and anti-inflammatory cytokines, polymorphism

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