ПОЛИМОРФИЗМ ГЕНА TNFAIP3 (T380G) И ЭКСПРЕССИЯ TNFAIP3 У БОЛЬНЫХ БРОНХИАЛЬНОЙ АСТМОЙ

Abstract

The single nucleotide polymorphism (T380G) and the degree of expression of the TNFAIP3 gene encoding the ubiquitin-modifying factor A 20, providing an inhibitory effect on the intensity of the immune response of TLR4-mediated signals, were studied. Materials and methods. 84 patients with bronchial asthma of varying severity (14 patients with mild, 49 with moderate and 21 with severe) and 52 practically healthy controls were examined. The determination of single nucleotide polymorphism of the TNFAIP3 (T380G) gene was carried out by the method of allelic discrimination using real-time polymerase chain reaction. Expression of the TNFAIP3 gene was determined by the concentration to DNA relative to the level of expression of the reference GAPDH gene also by real-time PCR. Results. In the study of the TNFAIP3 gene polymorphic marker (T380G), the level of homozygosity for the dominant trait (TT) was 88.1% in patients with asthma, and 88.1% in healthy donors, for the recessive (GG) trait, 3.6% and 4, respectively. 8% (p <0,05), the degree of heterozygosity (TG) was 8.3% and 7.1% in the control group (p <0.05), ), which does not allow at this stage to consider the participation of this single nucleotide polymorphism in the genesis of asthma proven. Expression of the TNFAIP3 gene in both groups ranged from 0 to 5 units, including in patients of group 1 with mild asthma, the expression level of this gene was 2.36 (1.89; 2.94) units. and did not significantly differ from the value of this indicator in the control group (p> 0,05). In group 2 of patients with persistent asthma of moderate severity, the expression of the TNFAIP3 gene was 1.08 (0.87; 1.38) units, which is significantly lower than in patients of the control group (p 0,05). Conclusion. Low expression of the TNFAIP3 gene, leading to inadequate production of factor A 20, observed in severe asthma, can lead to a decrease in the function of the epithelial barrier to classical (ET) and potential ligands that activate type 4 toll-like receptors, followed by activation of intracellular NF-κB and the synthesis of proinflammatory cytokines that play a decisive role in the formation of chronic inflammation in asthma. This work was supported by the RFBR grant No. 19-315-90116.