Abstract
Bronchial asthma (BA) has a polygenic nature, and the onset of its manifestation and features course is realized due to the influence of genetic factors. This study aimed to investigate the effect of polymorphisms of the genes of the phase II detoxification system and genes of the cardiovascular tone on the severity of asthma in children. The study included 163 children aged 5–18 years: 38 with severe asthma, 69 with moderate asthma, and 56 with mild asthma. A molecular genetic study was conducted to determine the frequency of gene propagation and gen-gene interaction by GSTT1, GSTM1, GSTP1, ACE, eNOS, AT2R1, NAT2 genes at different severity of bronchial asthma. Found that in the prediction of the severity of asthma special place belongs to the analysis of the combination of genotypes. Independent effects were found for AT2R1 and ACE gene polymorphisms. The ACE (I / D) / AT2R1 (A1166C) / eNOS (T786C) / eNOS (4b / 4a) four-locus model was developed to predict the severe BA course and the need for additional analysis of the interaction of AT2R1 (A1166C) and eNOS (T786C), eNOS (T786C) genes was demonstrated (4b4a) and GSTT1. The risk of developing severe BA has been demonstrated for the combination of 1166SS + 786TT, 1166CC + 786TC genotypes by AT2R1 (A1166C) and eNOS (T786C) genes, and the reduction of this risk for combinations of eNOS (4b4a) 4b4b + GSTT1 genotypes. In moderate asthma, combinations of ACE genotypes DD + AT2R1 1166SS and AT2R1 313AA + GSTP1 1166SS were reliable risk markers for severe asthma. AT2R1 gene polymorphism was the leading marker in more severe asthma. A marker of severe BA was also found for the heterozygous 857GA polymorphism of the NAT2 gene (G857A). Conclusions. The influence of ACE (I / D), AT2R1 (A1166C), eNOS (T-786C), NAT2 (G857A), GSTT1, and GSTP1 gene polymorphisms on the severity of asthma in children has been established.
Highlights
Bronchial asthma (ВА), as a genetically determined disease, heterogeneous in its clinical manifestations, pathophysiological and immunopathological mechanisms, is characterized by chronic inflammation of the respiratory tract, manifested by the recurrent respiratory symptoms, such as wheezing, shortness of breath, chest tightness and cough, which can vary in intensity and occur together with variable airway obstruction [1]
In order to predict the course of bronchial asthma in children, it is advisable to perform genetic testing and to determine polymorphisms of genes of the enzymes of the phase II detoxification system (GSTT1, GSTM1, GSTP1, NAT2) and cardiovascular tone genes (AT2R1, angiotensin converting enzyme (ACE), eNOS)
The severity of bronchial asthma in children is depends on the ACE (I/D) and AT2R1 (A1166C) genes, and is can be formed by the interaction of the eNOS, NAT2 (G857A), GSTT1 and GSTP1 genes
Summary
Bronchial asthma (ВА), as a genetically determined disease, heterogeneous in its clinical manifestations, pathophysiological and immunopathological mechanisms, is characterized by chronic inflammation of the respiratory tract, manifested by the recurrent respiratory symptoms, such as wheezing, shortness of breath, chest tightness and cough, which can vary in intensity and occur together with variable airway obstruction [1]. The study found a connection between total serum IgE level and the HLA-DRB1 gene in the class II major histocompatibility complex region on chromosome 6 This locus was not associated with asthma and it was suggested that an increase of IgE levels in serum plays a minor role in asthma development. These studies have proved that asthma, both genetically and phenotypically, is a highly heterogeneous disorder, and asthma susceptibility genes are broadly divided into three categories related to: 1) immune system functioning, 2) biology and mucous membrane functions, and 3) lungs function and disease expression [3, 4]. The genetic architecture of BA is being considered in the context of a polygenic system characterized by the additive effect of the individual genes, each of which is virtually individually incapable of causing the disease [5, 6], but internal and external factors are capable of altering gene expression directly or indirectly through the epigenetic changes [7, 8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
