Association of gene polymorphism and cytokine content in the blood serum in children with allergic bronchial asthma

Abstract

The study of genes controlling cytokine activities of is among important tasks when assessing predisposition and revealing pathogenetic links of initiation and course of clinical disorders. Aberrant production of cytokines and dysregulation of immune response may be considered genetic predictors associated with differentiation and functioning of T helpers, being of decisive importance in pathogenesis of pediatric allergic bronchial asthma. Our objective was to evaluation of associations between polymorphic genotypes and serum levels of cytokines of various T helper profiles in the children with allergic bronchial asthma. We have observed 175 children aged 3 to 11 years. Of them, we have examined 75 patients diagnosed with allergic bronchial asthma (ABA) as well as 100 healthy children matched for age and gender. All children underwent general clinical and allergological examination. The contents of cytokines attributed to Th1, Th2 and Th17 profiles were determined in blood serum by means of ELISA technique. DNA samples isolated from peripheral venous blood were used for molecular genetic analysis. Using allele-specific PCR technique, the following mutation points were investigated: IFN (T-874 A), IL-4 (C-589 T), IL-6 (C-174 G), IL-17A (G- 197 A), TNF (G-308 A). The analysis of distribution and occurrence of the cytokine gene polymorphisms was carried out, and the odds ratio of the disease risk were calculated. Statistical data processing was carried out using the program Statistica 10 by methods of descriptive, parametric and non-parametric statistics, comparison of unrelated groups was performed by qualitative characteristics of HardyWeinberg equilibrium, and with Chi-square test ( 2). These studies have revealed differences in patterns and occurrence of polymorphic genotypes associated with aberrant production of cytokines typical for various Th profiles among the children with allergic bronchial asthma. A comparative analysis of the mutant allele frequencies and cytokine genotypes of various Th profiles, along with determination of the cytokine contents in blood serum of children with allergic bronchial asthma revealed a predominance of homozygous IFN 874A, IL-4 589T, IL-6 174G, IL-17A 197A, and TNF 308A genotypes. Studies of gene polymorphisms, features of production and content of the cytokines specific for T helpers 1, T helpers 2, T helpers 17 profiles in bronchial asthma in the children revealed differences in distribution and occurrence of mutant alleles associated with aberrant cytokine production, variable risk of developing allergic pathology and development of the distinct disease phenotype.