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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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Larysa Petrivna Sydorchuk, Olga Petrivna Bukach, Olexandr Ivanovych Fediv, Andrii Ruslanovych Sydorchuk, Oksana Anatoliivna Petrynych, Tetyana Vasilyvna Kazantceva, Larysa Vasilyvna Melnychuk, Liviya Vasilyvna Nikyfor, Marianna Mykolayivna Semianiv, Yulia Vasilyvna Repchuk, Michael Ivanovich Sheremet, Ruslan Igorovych Sydorchuk, Yulia Mykolayivna Yarynych, Oksana Mykolayivna Korovenkova and Vasil Vasilevich Boyko

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