The Role of Hereditary Predisposition (Polymorphic Markers of Glutathione-S-Transferase, Catalase, Endothelial Nitrogen Oxide Synthase Genes) and Some Adverse Environmental Factors in the Development of Broncho-Obstructive Pathology in Children Living in Radioactively Contaminated Areas

Abstract

Objective: summarizing the results of many years of research by the authors on the influence of gene polymorphisms encoding xenobiotic biotransformation enzymes (GSTТ1, GSTM1, GSTР1), antioxidant protection (С-262Т of the catalase gene), endothelial nitric oxide synthase (4a/4b VNTR polymorphism of the eNOS gene), and some environmental factors on the occurrence of broncho-obstructive disorders and the development of bronchial asthma in children, residents of radioactively contaminated areas. Materials and methods. The examined school-aged children were residents of radioactively RCA who had no clinical signs of respiratory pathology. Deletion polymorphism of catalase gene (CAT C-262T), polymorphism of glutathione-Stransferase gene (GSTТ1, GSTM1, GSTР1) and the polymorphism in the 4th intron (4a/4b) of the eNOS gene were studied in the molecular genetics laboratory of the State Institution «Reference Center for Molecular Diagnostics of Public Health Ministry of Ukraine». Molecular genetic studies were performed by polymerase chain reaction. The study of the ventilation lung capacity was carried out by the method of computer spirometry based on the data of the «flow–volume» loop analysis. A pharmacological inhalation test with a bronchodilator drug which affects the β2-adrenergic receptors of the lungs was used to detect early changes in the ventilatory lung capacity – bronchial hyperreactivity. Results and conclusions. One of the leading mechanisms, due to which the implementation of hereditary predisposition to bronchial asthma in children living in radioactively contaminated areas is the polymorphism of certain genes of glutathione-S-transferase, catalase, endothelial nitric oxide synthase. With such polymorphic variants of the GST genes, isoforms of enzymes with reduced activity are produced, which limits their ability to effectively neutralize free radicals, which are formed in excess when free radical oxidation processes are activated due to the constant intake of radionuclides with a long half-life into the body of children. Unfavorable factors that increase the risk of developing broncho-obstructive disorders and the likelihood of their implementation in the form of bronchial asthma in children, residents of radioactively contaminated areas, have been identified. It has been established that among them the leading role is played by hereditary predisposition to this disease. On the part of the child, such negative factors were unfavorable conditions of intrauterine development, the presence of signs of exudativecatarrhal diathesis, manifestations of allergies and frequent respiratory diseases from the first months of life. Key words: children, radioactively contaminated areas, risk factors, bronchial asthma, polymorphism of glutathioneS-transferase, catalase, and endothelial nitric oxide synthase genes.