Iemets O. The characteristics of the clinical course of atopic diseases in children related to the polymorphisms of genes that encode proteins of lysosomal and proteasomal proteolysis

This dissertation is dedicated to solving the task of improving the effectiveness of the prognosis of risks, course and treatment of atopic diseases by studying the influence of the single-nucleotide polymorphisms in the ATG5 gene and the POMP gene on the clinical course of asthma, atopic dermatitis and allergic rhinitis in children. The minor T allele of rs510432 in the ATG5 gene was identified in patients with atopic diseases significantly more often than in healthy children (?2 = 6.36, р < 0.05). The minor allele of the ATG5 gene was associated with the increased risk of the early manifestation of asthma (in children up to 3 years old, р < 0.05). The results of the logistic regression demonstrated that the risk of atopic diseases in children with minor genotype is 2.4 times higher than in carriers of the CC genotype. The average values of FEV1 in asthma patients with minor genotype was significantly lower than in carriers of major genotype (Q = 2.71, р < 0.05). Antagonistic interaction between single nucleotide polymorphisms rs510432 in ATG5 and rs4769628 gene POMP was determined. Single-nucleotide polymorphism in POMP gene was associated with the reduced risk of developing atopic diseases. 62.26 % of patients and 53.06 % of the control group had major allele of rs4769628 in POMP. 33.67 % and 37.76 %, respectively, had heterozygous allele. Minor genotype GG was not detected in children with atopic diseases, 9.18 % of healthy children are carriers of the minor allele (р < 0.05). The benefit of testing for both the single nucleotide polymorphism rs510432 in ATG5 and the rs4769628 gene POMP was firmly established with regard to the treatment effectiveness prognosis in children with atopic diseases.