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Title: 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.
Author: Stepanova YI, Kolpakov IY, Vdovenko VY, Zigalo VM, Al'okhina SM, Kondrashova VH, Leonovych OS.
Journal: Probl Radiac Med Radiobiol; 2021 Dec; 26():449-463. PubMed ID: 34965566.
Abstract:
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. Оne 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. Meta roboty: vyznachyty vplyv spadkovoï skhyl'nosti, polimorfizmu geniv GSTT1, GSTM1, GSTP1 i chynnykiv navko-lyshn'ogo seredovyshcha na rozvytok bronkhial'noï astmy u diteĭ – meshkantsiv radioaktyvno zabrudnenykh tery-toriĭ.Materialy ta metody. Obstezheni dity shkil'nogo viku – meshkantsi radioaktyvno zabrudnenykh terytoriĭ, khvori nabronkhial'nu astmu, ta ti, iaki ne maly klinichnykh oznak patologiï organiv dykhannia. Na pidstavi vyvchennia anamnes-tychnykh danykh i medychnoï dokumentatsiï vyznachaly genetychni, medyko-biologichni ta sotsial'ni faktory ryzyku. Me-todom komp’iuternoï spirometriï otsiniuvaly stan ventyliatsiĭnoï spromozhnosti legeniv. Molekuliarno-genetychnidoslidzhennia provodyly z vykorystanniam metodiv polimeraznoï lantsiugovoï reaktsiï (PLR) i polimorfizmu dov-zhyny restryktsiĭnykh fragmentiv (PDRF) dlia podal'shogo analizu. Rezul'taty. Molekuliarno-genetychni doslidzhennia rozpodilu genotypiv i chastot polimorfnykh variantiv genivGSTT1, GSTM1, GSTP1 provedeni u diteĭ, iaki meshkaiut' za umov tryvalogo nadkhodzhennia do organizmu 137Cs kharchovy-my lantsiuzhkamy. Vstanovleno, shcho u diteĭ, khvorykh na bronkhial'nu astmu, sposterigaiet'sia tendentsiia do pidvyshchen-nia chastoty deletsiĭnogo varianta geniv GSTT1 i GSTM1 v porivnianni z dit'my, iaki ne maly patologiï bronkhiv ta le-geniv. Doslidzhennia rozpodilu polimorfnykh variantiv 313AG gena GSTP1 vyiavylo u diteĭ, khvorykh na bronkhial'nuastmu, dostovirne pidvyshchennia chastoty AG-genotypu, porivniano z pokaznykamy referentnoï grupy. Vyznacheninespryiatlyvi chynnyky, shcho pidvyshchuiut' ryzyk rozvytku bronkhoobstruktyvnykh porushen' ta ĭmovirnist' ïkh re-alizatsiï u vygliadi bronkhial'noï astmy u diteĭ – meshkantsiv radioaktyvno zabrudnenykh terytoriĭ. Vstanovleno,shcho sered nykh providnu rol' vidigraie spadkova skhyl'nist' do ts'ogo zakhvoriuvannia. Z boku dytyny takymy nega-tyvnymy chynnykamy vyiavylysia nespryiatlyvi umovy vnutrishn'outrobnogo rozvytku, naiavnist' oznak eksudatyv-no-kataral'nogo diatezu, proiaviv alergiï ta chastykh respiratornykh zakhvoriuvan' z pershykh misiatsiv zhyttia. Vstanov-leno, shcho ryzyk rozvytku bronkhial'noï astmy suttievo zrostav u diteĭ z deletsiĭnymy genotypamy geniv GSTT1 iGSTM1; vyznacheno pidvyshchennia ryzyku rozvytku bronkhial'noï astmy u diteĭ pry poiednanni 313AG polimorfizmugena GSTR1 z deletsiĭnym polimorfizmom gena GSTT1 abo GSTM1.Vysnovok. Odnym iz providnykh mekhanizmiv, zavdiaky iakomu vidbuvaiet'sia realizatsiia spadkovoï skhyl'nosti vbronkhial'nu astmu u diteĭ, iaki meshkaiut' za umov postiĭnogo nadkhodzhennia do organizmu radionuklidiv z tryva-lym periodom napivrozpadu, ie polimorfizm pevnykh geniv glutation-S-transferazy, a same, deletsiĭnyĭpolimorfizm geniv GSTT1, GSTM1 i 313AG ta poliforfizm gena GSTP1.

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