Frolova S. Effectiveness of determining the risk factors for the development of age-related macular degeneration

The dissertation is devoted to the problem of increasing the effectiveness of diagnosis and predicting the development of age-related macular degeneration by determining the role of risk factors and genetic polymorphism of candidate genes (ARMS2, CFH and VEGFA) in its occurrence and progression within patients of the Ukrainian population. In course of this dissertation research the main task of the work was to study the role of polymorphism of candidate genes (ARMS2, rs10490924, CFH, rs800292, VEGFA, rs2010963 and rs699947) in the predisposition to the occurrence and progression of various stages of age-related macular degeneration in Ukraine. This dissertation research gave the grounds to establish for the first time in Ukraine the pathogenic significance of polymorphisms ARMS2, rs10490924; CFH, rs800292; VEGFA, rs2010963 and rs699947 and to determine an association with the development of age-related macular degeneration for the polymorphic genotypes alleles rs10490924 of gene ARMS2, rs 800292 of gene CFH and rs2010963 of gene VEGFA. It was established that there is an association between the development of the "dry" form of AMD and the pathognomonic changes in the morphological structure of the maculae for the alleles rs2010963 of gene VEGFA . It was established in course of the studies that in case of stratification by the presence of the "wet" form of AMD in Ukraine the force of association increased for polymorphisms rs 10490924 of gene ARMS2 and rs800292 of gene CFH. For polymorphism rs2010963 of gene VEGFA there was an association with the "wet" form for alleles, as well as for genotypes. For the first time a mathematical model was developed for predicting genetic predisposition and probable risk of "wet" form of AMD in the light of the results on the association between genotypes and alleles of polymorphisms: rs10490924 of gene ARMS2, rs800292 of gene CFH, rs2010963 of gene VEGFA and rs699947 of gene VEGFA and markers of the morphological structure of maculae within the patients with the " wet" form of age-related macular degeneration. It was established that in course of comparing the groups with "dry" and "wet" AMD as between themselves the polymorphisms rs800292 of gene CFH and rs699947 of gene VEGFA determined the form of AMD. It was established that in case of the "dry" form of AMD the polymorphisms rs10490924 of gene ARMS2 and rs800292 of gene CFH had a pathogenic significance, since they contributed to hypercholesterolemia, atherogenic dyslipidemia and blood condensation. Furthermore, we have developed a mathematical model for predicting the age of development of AMD, which includes the haplotype.