Clinical and immunological manifestations of gene polymorphisms cytokines in controlled and uncontrolled bronchial asthma

Author:

Suprun E. N.1ORCID,Suprun S. V.2ORCID,Nagovitsina E. B.2ORCID,Galyant O. I.2ORCID,Lebed’ko O. A.2ORCID

Affiliation:

1. Khabarovsk Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration Research Institute of Maternity and Childhood Protection; Far-Eastern State Medical University

2. Khabarovsk Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration Research Institute of Maternity and Childhood Protection

Abstract

Introduction. Bronchial asthma (BA) is a multifactorial disease, but its pathogenesis in children is based on atopic inflammation, which is what modern therapies are aimed at combating; less attention is paid to factors of nonspecific inflammation, but they also affect the controllability of the pathological process. The regulation of any inflammation is carried out primarily by cytokines, therefore this work is devoted to the study of polymorphisms of genes for cytokines of nonspecific inflammation.Aim. To explore the association between cytokine gene polymorphisms and clinical immunological features of uncontrolled asthma.Materials and methods. We examined 167 children with asthma, who were divided into groups with and without complete disease control, according to the standard of clinical guidelines for asthma. Additionally, mononucleotide substitutions in the cytokine genes were determined: IL4-C589T (rs2243250), IL6-C174G (rs1800795), IL10-G1082A (rs1800896), IlL10-C592A (rs1800872), IL10- C819T (rs1800871), IL12B-A118 8C (rs3212227) , TNFα- G308A (rs1800629), serum cytokine levels: IL4, 5, 6, 7, 8, 9, 10, 18 and TNFα; standard immunogram indicators: subpopulations of lymphocytes, neutrophil phagocytosis and levels of Ig A, M, G, E.Results and discussion. It was determined that each of the clinically significant mononucleotide substitutions forms a unique cytokine and immune profile that is phenotypically realized in the clinical manifestations of the disease. It has been proven that mononucleotide substitutions IL10-C592A, TNFα- G308A contribute to better control with a tendency to milder asthma; children with the IL6-C174G polymorphism experience more severe disease with a tendency toward decreased control. In addition, mononucleotide substitutions in the genes of signaling molecules of the immune system modify atopic inflammation, weakening (IL10-C592A, TNFα- G308A) or enhancing (IL6-C174G) it, which leads to a change (decrease or increase) in the dose of TGCS, respectively.Conclusion. Thus, determination of IL6-C174G (rs1800795), IL10-C592A (rs1800872), TNFα- G308A (rs1800629) polymorphisms in children with ВА helps to identify a risk group for severe and uncontrolled disease, as well as to personalize therapy. 

Publisher

Remedium, Ltd.

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