RESUMO
OBJECTIVE: to determine the influence of hereditary predisposition, polymorphism of GSTT1, GSTM1, GSTP1 genes andenvironmental factors on the development of bronchial asthma in children - residents of radioactively contaminat-ed 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 riskfactors were determined based on the study of anamnestic data and medical records. Ventilation lung capacity wasassessed by the method of computer spirometry. Molecular genetic studies were carried out using polymerase chainreaction (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 thegenes GSTT1, GSTM1, GSTP1 were performed in children living under long-term intake of 137Cs by food chains. It wasfound that in children with BA the tendency to frequency of the deletion variant of the GSTT1 and GSTM1 genes incomparison with children without bronchial and pulmonary pathology was increased. The study of distributing theGSTP1 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 bron-choobstructive 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 hereditarypredisposition to this disease. On the part of the child, such negative factors were unfavorable conditions of fetaldevelopment, the presence of signs of exudative-catarrhal diathesis, manifestations of allergies and frequent respi-ratory diseases from the first months of life. It was found that the risk of developing BA was significantly increasedin children with the GSTT1 and GSTM1 gene deletion genotypes; an increased risk of developing BA in children witha combination of the GSTP1 A313G gene polymorphism with deletion polymorphism of the GSTT1 or GSTM1 gene wasdetermined. Сonclusion. Ðne of the leading mechanisms, due to which there is a realization of hereditary predisposition tobronchial asthma in children living under constant intake of radionuclides with a long half-life, is the polymorphismof certain glutathione-S-transferase genes, namely, GSTT1, GSTM1 and A313G gene deletion polymorphism and GSTP1gene polymorphism.
Assuntos
Asma/genética , Asma/fisiopatologia , Radioisótopos de Césio/efeitos adversos , Acidente Nuclear de Chernobyl , Predisposição Genética para Doença , Glutationa Transferase/genética , Polimorfismo Genético/efeitos da radiação , Exposição à Radiação/efeitos adversos , Adolescente , Asma/epidemiologia , Estudos de Casos e Controles , Criança , Feminino , Genótipo , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Humanos , Masculino , Fatores de Risco , Ucrânia/epidemiologiaRESUMO
OBJECTIVE: to determine the relationship between polymorphisms of glutathione S-transferase gene family andbronchial hyperreactivity in children living in radioactively contaminated areas. MATERIALS AND METHODS: School age children-residents of radioactively contaminated areas (RCA), without clinicalsigns 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 studyof the GSTP1 gene A313G polymorphism. The ventilation lung capacity was examined by the pneumotachographicmethod according to the analysis of «the flow-volume¼ loop. The pharmacologic inhalation test with bronchodilator drug, affecting the ß2-adrenergic lung receptors was used to detect the early changes in the ventilation lungcapacity - 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 inRCA than in children without bronchial hyperreactivity and children of the control group. The frequency of GSTT1deletion 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 fordeveloping bronchial hyperreactivity in children living under adverse environmental conditions, including radioactively contaminated areas.