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Cytokines cascade changes in patients with rheumatoid arthritis depending on endothelial no-synthase (T-786C) genes polymorphism

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ABSTRACT

Introduction. Rheumatoid arthritis (RA) is a mul- tifactorial disease with genetic factors involvement. Objective: to evaluate the alleles and genotypes fre- quency of eNOS gene T-786C polymorphism (rs 2070744) in patients with RA and their association with RA severity and cytokine profile changes.

Methods. The eNOS T-786C gene polymorphism was analysed by polymerase chain reaction in 60 patients with RA and 20 healthy individuals. The cytokines level (interleukins -6, -10, -12, and -18) in pg/ml was detected in blood plasma by Immuno-enzyme method. Results. Wild T-allele dominates over mutant C-allele in the population by 30% (P<0.001). Relative frequency of patients with a high IL-12, IL-6 level production and decreased IL-10 production prevails among the TT- and TC-genotypes carriers (P<0.05). Plasma concentrations of pro-inflammatory cytokines (IL-12, IL-18, IL- 6) in RA patients were 1.96-4.63 times higher than in the control group (P≤0.049), and anti-inflammatory IL-10 was lower 1.68-2.73 times (P≤0.01). Moreover, the IL- 12 and IL-6 plasma content in CC-genotype carriers was higher than in the TT- and TC-genotypes carriers (P<0.05). Immune response imbalance in RA patients is characterized by cellular Th1 immunity activation and insufficient activity of humoral Th2 stipulated by an excessive production of IL-12, IL-18 and IL-6 in CC-genotype carriers and lower content of anti-inflam- matory IL-10 in C-allele carriers of eNOS gene, that indicates a presence of acute inflammatory process, high activity of non-specific anti-infectious immune protection and low/insufficient general body reactivity.

Conclusions. Genotypes of the analysed eNOS gene are not additional risk factors of cytokine production changes in RA patients.

Keywords: eNOS gene (rs2070744), rheumatoid ar- thritis, cytokine.

Abbreviations:

eNOS – endothelial nitric oxide synthase IL – interleukin

NO – nitric oxide

RA – rheumatoid arthritis

TNF-a – tumour necrosis factor alpha

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