The Research of Gene Polymorphism of Glutathione-S-Transferase Family Association: Gstm1, Gstт1 and Gstр1 With the Development of Bronchopulmonary Dysplasia and Necessity in Respiratory Support

Objective. to determine the relationship between polymorphisms of glutathione S-transferase gene family and bronchial hyperreactivity in children living in radioactively contaminated areas. Materials and methods. School age children-residents of radioactively contaminated areas (RCA), without clinical signs of respiratory pathology were examined. Molecular genetic studies were carried out by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for further analysis. The GSTT1, GSTM1 gene deletion polymorphism was investigated using multiplex PCR. PCR and PCR-RFLP analyses were performed in the study of the GSTP1 gene A313G polymorphism. The ventilation lung capacity was examined by the pneumotachographic method according to the analysis of «the flow–volume» loop. The pharmacologic inhalation test with bronchodilator drug, affecting the β2-adrenergic lung receptors was used to detect the early changes in the ventilation lung capacity – the bronchial hyperreactivity (latent and nonlatent bronchospasm). Results. Molecular genetic studies showed that the GSTM1 gene deletion genotype and the GSTP1 gene A313G polymorphism were found significantly more often in the subgroup of children with bronchial hyperreactivity living in RCA than in children without bronchial hyperreactivity and children of the control group. The frequency of GSTT1 deletion polymorphism did not have a statistically significant difference in all subgroups. Conclusions. The GSTM1 gene deletion polymorphism and the GSTP1 gene A313G genotype may be a risk factor for developing bronchial hyperreactivity in children living under adverse environmental conditions, including radioactively contaminated areas. Key words: children, radioactively contaminated areas, bronchial hyperreactivity, glutathione-S-transferase gene polymorphisms.

Section: Methodsmentioning

confidence: 99%

Section: Objectiveunclassified

Section: клінічні дослідженняmentioning

confidence: 99%

mentioning

confidence: 99%

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Molecular Genetic Aspects of Bronchial Hyperreactivity in Children – Residents of Radioactively Contaminated Areas

Stepanova

Kolpakov

Vdovenko

et al. 2020

Role of Genetic Predisposition, Gene Polymorphism of Glutathione-S-Transferase (Gstt1, Gstm1, Gstp1) and Some Adverse Factors in Development of Bronchial Asthma in Children – Residents of Radioactively Contaminated Areas

Stepanova¹,

Kolpakov²,

Vdovenko³

et al. 2021

Objective: to determine the influence of hereditary predisposition, polymorphism of GSTT1, GSTM1, GSTP1 genes and environmental factors on the development of bronchial asthma in children – residents of radioactively contaminated areas. Materials and methods. School-age children-residents of radioactively contaminated areas with bronchial asthma, and those without clinical signs of respiratory pathology were examined. Genetic, medical, biological and social risk factors were determined based on the study of anamnestic data and medical records. Ventilation lung capacity was assessed by the method of computer spirometry. Molecular genetic studies were carried out using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for further analysis. Results. Molecular genetic studies of the distribution of genotypes and frequencies of polymorphic variants of the genes GSTT1, GSTM1, GSTP1 were performed in children living under long-term intake of 137Cs by food chains. It was found that in children with BA the tendency to frequency of the deletion variant of the GSTT1 and GSTM1 genes in comparison with children without bronchial and pulmonary pathology was increased. The study of distributing the GSTP1 A313G gene polymorphic variants revealed in children with BA a significant increase in the frequency of AG-genotype, compared with the data of reference group. Adverse factors that increase the risk of developing bronchoobstructive disorders and the probability of their implementation in the form of bronchial asthma in children residents of RCA have been identified. It is 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 fetal development, the presence of signs of exudative-catarrhal diathesis, manifestations of allergies and frequent respiratory diseases from the first months of life. It was found that the risk of developing BA was significantly increased in children with the GSTT1 and GSTM1 gene deletion genotypes; an increased risk of developing BA in children with a combination of the GSTP1 A313G gene polymorphism with deletion polymorphism of the GSTT1 or GSTM1 gene was determined. Сonclusion. Оne of the leading mechanisms, due to which there is a realization of hereditary predisposition to bronchial asthma in children living under constant intake of radionuclides with a long half-life, is the polymorphism of certain glutathione-S-transferase genes, namely, GSTT1, GSTM1 and A313G gene deletion polymorphism and GSTP1 gene polymorphism. Key words: children, radioactively contaminated areas, risk factors, bronchial asthma, glutathione-S-transferase gene polymorphism.

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

Kolpakov,

Vdovenko,

Zyhalo

et al. 2023

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.