The dissertation is devoted to increasing the effectiveness of prevention, early diagnosis, and prediction of the manifestation and severity of dysmetabolic nephropathy in children by clarifying the genetic and epigenetic factors in its pathogenesis.
A consolidated integrated approach to establishing the sequential links of the pathogenesis of dysmetabolic nephropathy in children with a defined genetic background and under the influence of established negative epigenetic factors that acted on the embryo and fetus antenatally and postnatally is presented.
The hypothesis that numerous ante- and postnatal epigenetic factors play a leading role in the initiation of dysmetabolic nephropathy in children has been confirmed, antenatal and postnatal epigenetic risk factors have been comprehensively studied and established, which, due to the additive effect, caused the formation of undifferentiated connective tissue dysplasia syndrome in children, which became the basis for the formation of dysmetabolic nephropathy in children and caused a predisposition to its more severe course.
The most significant antenatal epigenetic factors were: the threat of early pregnancy termination, gestosis of the first and second half of pregnancy, anemia of the pregnant woman, alcohol consumption and smoking of the parents, the mother's work during pregnancy at the computer, the presence of chronic diseases in the mother, the parents' contact with industrial dust and noise, and heavy physical labor, which lead to fetal hypoxia. The leading postnatal epigenetic factors that caused not only the manifestation, but also a more severe course of dysmetabolic nephropathy were: low body weight at birth, early artificial feeding, frequent acute respiratory infections, atopic diathesis and physiological jaundice, and in later life - the presence of concomitant diseases, such as chronic tonsillitis, dental caries, frequent acute respiratory infections, chronic gastritis, atopy and chronic cholecystitis, which caused a significant number of children with a more severe course of dysmetabolic nephropathy to lag in physical development. It has been established that the genetic factors for the implementation of dysmetabolic nephropathy are the carrier of the heterozygous genotype of the polymorphic locus Taq I of the VDR3 gene Tt,, the carrier of the heterozygous genotype of the polymorphic locus ApaI of the VDR3 gene AA by a child is associated with the risk of developing dysmetabolic nephropathy. The risk of developing dysmetabolic nephropathy is highest in children with the TtAA haplotype. Carriership of deletion alleles of the GSTT1 0/0 and GSTM1 0/0 genes is associated with a predisposition to dysmetabolic nephropathy, deletion alleles of the GSTT1 0/0 and GSTM1 0/0 genes as a modifier gene in the pathogenesis of dysmetabolic nephropathy.
