State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine», 53 Yuriia Illienka Str., Kyiv, 04050, Ukraine.
Probl Radiac Med Radiobiol. 2021 Dec;26:449-463. doi: 10.33145/2304-8336-2021-26-449-463.
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.
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.
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.
确定遗传易感性、GSTT1、GSTM1、GSTP1 基因多态性和环境因素对放射性污染地区儿童支气管哮喘发展的影响。
对放射性污染地区有支气管哮喘和无呼吸道病理临床征象的学龄儿童进行检查。基于病史资料和病历研究,确定遗传、医学、生物学和社会危险因素。通过计算机肺活量测定法评估通气肺容量。采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)进行分子遗传研究,以进一步分析。
对长期通过食物链摄入 137Cs 的儿童进行 GSTT1、GSTM1、GSTP1 基因基因型和多态性变异频率的分子遗传研究。结果发现,与无支气管和肺部病理的儿童相比,BA 患儿 GSTT1 和 GSTM1 基因缺失变异的频率有增加的趋势。对 GSTP1 A313G 基因多态性变异的分布研究表明,与参考组数据相比,BA 患儿 AG 基因型的频率显著增加。确定了增加儿童发生支气管阻塞性疾病的风险和以支气管哮喘形式实施的概率的不利因素,这些因素是 RCA 地区儿童的危险因素。结果表明,遗传易感性在其中起着主导作用。在儿童方面,这些不利因素是胎儿发育不良、存在渗出性卡他素质、过敏表现和从生命的最初几个月开始频繁发生呼吸道疾病等不利条件。结果发现,具有 GSTT1 和 GSTM1 基因缺失基因型的儿童发生 BA 的风险显著增加;具有 GSTP1 A313G 基因多态性与 GSTT1 或 GSTM1 基因缺失多态性组合的儿童发生 BA 的风险增加。结论:在持续摄入长半衰期放射性核素的情况下,导致儿童遗传易感性发生支气管哮喘的一个主要机制是某些谷胱甘肽-S-转移酶基因的多态性,即 GSTT1、GSTM1 和 A313G 基因缺失多态性和 GSTP1 基因多态性。