Features of the immune profile and polymorphism of candidate genes in children population of an industrially developed region with excessive contamination of the biological medium with mercury

Abstract

Introduction. Analyzing the negative impact of technogenic chemicals on the health of the children’s population of industrially developed regions is an urgent problem of preventive medicine. Excessive accumulation of mercury in the human body causes disadaptation changes in the immune regulation of physiological processes. Therefore, the analysis of the features of the immune profile associated with polymorphic variants of candidate genes as markers of early disorders of the child population’s health status is relevant in preserving the health of the population of industrialized regions. Materials and methods. A clinical and laboratory examination of the biological environment of 215 children aged 4-6 years was carried out. The observation group consisted of 133 people living in an industrially developed region. The comparison group consisted of 82 people living in a relatively clean territory. The level of contamination of the biological medium with mercury was determined by inductively coupled plasma mass spectrometry. Identification of CD3+CD4+ -, CD3+CD8+- and CD19+ - lymphocytes was performed by flow cytofluorometry. The study of the phagocytic activity of leukocytes was carried out using formalized ram erythrocytes. The level of IgG production was determined using radial immunodiffusion by Mancini, specific IgG to mercury was carried out using allergosorbent testing with an enzyme label. Identification of single-nucleotide polymorphic variants (SNP) of the GSTA4 (rs3756980), FOXP3 (rs3761547), MTR (rs1805087), TERT (rs10054203) genes was carried out by real-time PCR. Results. Children living near the territory of the chemical industry enterprise in conditions of mercury exposure at a level not exceeding hygienic standards are characterized by an increased level of mercury contamination of urine, exceeding the reference level and the level of the comparison group by 1.8 times (p<0.05). The immune profile of children in the observation group is characterized by a decrease in the CD4+/CD8+ immunoregulatory index due to the decline of CD3+CD4+ helpers and hyperproduction of CD3+CD8+ cytotoxic lymphocytes, inhibition of the phagocytic activity of leukocytes (percentage of phagocytosis, phagocytic number, phagocytic index) against the background of an increase in CD19+ lymphocytes, serum IgG and a marker of specific sensitization - IgG to mercury (p<0.05). Changes in the immune profile of children with an increased level of mercury contamination are associated with the C-allele and TC-heterozygous and CC-homozygous genotypes of the GSTA4 gene (rs3756980), the C-allele and CC-genotype of the FOXP3 gene (rs3761547), the A-allele and AA-genotype of the MTR gene (rs1805087) (OR>1, p<0.05), the G-allele and GG-genotype of the TERT gene (rs10054203) (p<0.05). These genes are responsible for the features of detoxification processes, immunoregulation and longevity programs. Conclusion. The established features of cellular (decrease in CD4+/CD8+ due to CD3+CD4+ deficiency with simultaneous increase in CD3+CD8+, inhibition of phagocytosis) and humoral (hyperproduction of IgG, specific IgG to mercury, CD19+) immunity associated with polymorphic variants of the glutathione S-transferase GSTA4 (rs3756980), transcription factor FOXP3 (rs3761547), MTR (rs1805087), TERT telomerase (rs10054203) in children with excessive contamination of the biological medium with mercury, a complex of immune and genetic markers of the effect and sensitivity of mercury exposure is formed.