The dissertation is devoted to the solution of one of the global medical and social problem in pediatrics, caused by a significant prevalence of childhood obesity in a urbanized society with the aim - to reduce the risk of insulin resistance within obesity in children with lactase gene polymorphisms (SNP LCT) by increasing the efficacy of obesity treatment based on studying the factors that trigger chronic inflammation. The novelty of this work is to study the factors that induce insulin resistance within obesity in children caused by a genetically determined impairment of lactose absorption, which's increase in the ratio leads to a specific inhibition of galactine 9, the main ligand receptor for T-cell apoptosis (Tim-3), and prolongs the inflammatory immune response of Th1- and Th17-type. It was proved that lactase gene genotype C/C 13910 in children with obesity had been determined 2 times more often than in children with physiological body weight. For the first time, associations have been identified between changes in the level of mRNA of galectin 9 expression and genotypes of the lactase gene in children’s obesity. It was firstly studied that the frequency of of maldigestion occurrence within obesity in children with different genotypes of the lactase gene, which had been investigated by a hydrogen breath test with lactose load (HBTLL), amounted to 65.9% in the genotype C/C 13910, with C/T 13910 genotype - 39.4%, within the genotype T/T 13910 - maldigesters of lactose had not been observed. The use of standard therapy in children with the genotype C/C 13910 without lactose maldigestion resulted in a significant decrease in median values of Gal-9 mRNA expression (1081.94 - before therapy and 392.58 - after therapy IU ΔmRNA Gal-9 / mRNA actin respectively; changes in the median with 95 % CI: -404.6 (-454.34 -330.97) and was equal to the mRNA Gal 9 expression in healthy children (313.34±19.7 IU ΔmRNA Gal- 9/mRNA actin). The scientifically based results of one-factor dispersion analysis (ANOVA) showed that the genotype of the lactase gene (F=6.69; p=0.002 and F=12.44; p<0.001) was influenced by the level of the HOMA-IR index and the HBTLL. The pairwise comparison of the insulin resistance indices formation among them, depending on the genotype LCT, revealed statistically significant higher levels of the indices under the genotype C/C 13910 (p<0.05 for pairwise comparisons of the C/C 13910 genotype with the others according to the Tukey’s criterion). For the first time, an assessment of the personality-emotional mental status and quality of life in adolescents, depending on the nutritional status caused by the genotypes of lactase, revealed a higher level of personal anxiety and the average level of reactive anxiety in children with genotype C/C 13910, compared to adolescents with genotypes C/T and T/T 13910. Quality of life in adolescent boys and genotype C/C 13910 was statistically significantly lower than the indicators of role-based functioning due to physical condition (RP) compared with boys with genotypes C/T and T/T 13910, p<0.05. Indicator of general health (GH) in obese girls associated with the genotype C/C 13910 was statistically significantly lower than GH, than in girls with the genotype C/T and T/T 13910, p<0.05. The maximal frequency of occurrence (87 %) of behavioral abnormalities was observed in children with genotype C/С 13910, and the minimum frequency was common for the genotype C/T 13910 (21 %). The innovative computer soft-ware "Low - lactose diet" for calculating a low-lactose diet provides the limitating the use of lactose to 12 g daily if the HBDLL index is <10 ppm. If the HBDLL indicator is in the range 10-19 ppm it is necessary to reduce the daily amount of lactose in the diet to 1 g and combined with a substitution therapy with exogenous lactase preparations if the HBDLL indicator > 20 ppm.In order to increase the efficacy of planning personalized preventive and rehabilitation measures within patients with overweight, it was proposed to use practical algorithms for predicting abnormal obesity in children with different genotypes of the lactase gene at the early diagnostic stage by physicians. As a result, the efficacy of therapy in the observation groups depends on the chosen treatment method in children with genotype C/C 13910 (with the difference between the groups according to the χ2 - criterion - p<0.001) demonstrates an equally high level of substitution enzyme therapy (90 %) and low-lactase diet (90.91 %), while the level of standard therapy efficacy is characterized as average.
Key words: obesity, children, genotypes of the gene of lactase, galectin 9, personality psychotypes, low-lactose diet, exogenous lactase.
