Genetic aspects of chronic lung diseases in children

Background. At the present stage, the study of the effect of vitamin D due to interaction with its receptor (vitamin D receptor - VDR) is fundamental for understanding the principles of the implementation of genomic and non-genomic effects of vitamin D on cells. Polymorphisms of genes encoding the vitamin D receptor (VDR) and vitamin D binding protein are considered as possible reasons for the variable effect of vitamin D in the implementation of the inflammatory process. In this regard, attention is shifted to the genetic basis of VDR regulation. At the same time, in assessing the variability of pathology and the response to pharmacotherapy with vitamin D, special attention was paid to the VDR gene BSMI (283 G>A). polymorphisms. Objective.Evaluation of the effect of polymorphic variants of vitamin D receptor genes on the course of chronic bronchopulmonary diseases in children. Methods. According to the purpose of the study, a comprehensive examination of 98 children with chronic lung diseases was carried out. Patients received treatment in the Pulmonary Department of the N.N. Silischeva Regional Children’s Clinical Hospital (Astrakhan) from 2016 to 2019. To solve the problem, all patients were divided into 2 groups. The first group was represented by children diagnosed with chronic bronchitis (n=30, 8.0±0.67 years) and obliterative bronchiolitis (n=12, 6.83+0.84 years). The second group included patients with diagnosed cystic fibrosis (n=34, 9.0+1.09 years), primary immunodeficiencies (n=12, 10.67+1.05 years) and malformations of the lung (n=10,6, 60+1.27), that is, patients with congenital defects of the mucociliary system. The study design was presented by several stages. At the first stage, the collection of clinical and anamnestic data of patients was carried out. The biochemical spectrum of the examination included the determination of blood serum total hydroxycalciferol by the enzyme immunoassay. The molecular genetic stage was represented by genotyping of the VDR gene BSMI (283 G>A) polymorphisms. At the final stage, the obtained results were processed using Microsoft office applications (Excel spreadsheets and the STATISTICA 10 program) using parametric and nonparametric methods depending on the distribution of a characteristic. Results. The A/A genotype of the VDR gene BSMI (283 G>A) polymorphism is a candidate for the development of CLD in children. The homozygous genotype A/A can be considered as protective in the implementation of severe exacerbation of the bronchopulmonary process, contamination and chronic seeding of highly pathogenic microflora in the biotope of the respiratory tract, inflation of pulmonary functional parameters and associated with a decrease in serum calcidiol values below 20 ng/mL in children with chronic lung diseases. The association of the major genotype G/G of the VDR gene BSMI (283 G>A) polymorphism with hereditary diseases of the bronchopulmonary system in females, with moderate exacerbations, a highly pathogenic profile of the respiratory tract microbiota, with a moderate incidence of irreversible morpho-functional changes in the form of bronchiectasis, a decrease in serum calcidiol level in the range of 21-30 ng/mL, in children with chronic lung disease was revealed. Conclusion. Thus, it was determined that the BSMI polymorphism (283 G>A) of the VDR gene is one of the possible polymorphisms that has a phenotypic effect on the course of chronic bronchopulmonary diseases in children.

BSMI (283 G>), vitamin A, chronic lung diseases, children, genes, vitamin D, vitamin D receptor, polymorphism, BSMI (283 G>)