Vyshtak N. Polymorphic variants of xenobiotics biotransformation genes in children from technologically polluted areas of Carpathians region

Thesis is devoted to a comprehensive study of detoxification systems: establishing of the impact of polymorphism of genes involved in the biotransformation of xenobiotics, the catalytic activity of enzymes encoded by them in susceptibility to certain diseases and characteristic of environmentally determined disorders in carriers of different genotypes of detoxifying enzymes gene CYP1A1, mEPHX, GSTM1, GSTT1, GSTP1, NAT2 under different environmental conditions. The differences of the alleles and genotypes frequencies between groups of children living in polluted areas and residents of clean area were not significant, as they belong to single ethnic group. CYP1A1 3801TC; mEPHX 415GG, GSTT1(del/del), GSTP1 313GG, NAT2 590AA and 857GA genotypes can be considered as markers of susceptibility to ecological diseases. For mEPHX 415AG heterozygous variant the protective effect was observed. The increase risk (OR=4,9-13,9) genotypes combination were established: CYP1A1 3801TC/GSTP1 313GG, GSTT1(del/del)/NAT2 590AA for metabolic nephropathy; GSTM1(del/del)/NAT2 857GA for thyroid hyperplasia; GSTT1(del/del)/NAT2 481CT for inflammation of the respiratory system; GSTT1(del/del)/NAT2 481CT for tonsil hypertrophy; GSTT1(del/del)/NAT2 481CT for gastrointestinal disorders. It has been revealed that the presence of low functionality alleles of GSTM1, GSTT1 and NAT2 genes leads to decreased activity of glutathione-S-transferase (GST) and N-acetyltransferase. In children with ecological disorders the increased activity of GST was observed. The enzymes activity in children living in environment with air pollution by Burshtyn TPP emissions was decreased. Recommendations for effective laboratory diagnosis of disorders and calculating of risk of pathological conditions in children were developed.