Problems of Radiation Medicine and Radiobiology

Ye. I. Stepanova, I. Ye. Kolpakov, V. Yu. Vdovenko, V. М. Zigalo, S. M. Alokhina,
V. H. Kondrashova, О. S. Leonovych

State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine», 53 Yuriia Illienka Str., Kyiv, 04050, Ukraine

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

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.

Problems of Radiation Medicine and Radiobiology.
2021;26:449-463. doi: 10.33145/2304-8336-2021-26-449-463

full text

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