StatusThe thesis was presented on the 14 December, 2012
Approved by NCAA on the 14 June, 2013
Abstract– 0.65 Mb / in romanian
– 0.64 Mb / in russian
Thesis structure: The thesis is written in Russian and consists of an introduction, 4 chapters, general conclusions and recommendations, bibliography of 178 titles and 8 annexes. The main text of the thesis comprises 114 pages, 19 figures and 23 tables. The basic results of the thesis were published in 21 scientific papers.
Field of research: 03.00.15 – Genetics.
The aim of study: to evaluate the efficiency of gene candidate polymorphisms as markers of ischemic stroke in the population of the Republic of Moldova.
Tasks:to analyze the prevalence of polymorphisms of F2, F5, GP1BA, PAI-1, ACE, ALOX5AP and PDE4D candidate genes in studied groups; to determine associations of polymorphic variants of genes that encode components of coagulation, fibrinolysis, endothelial function and inflammation with ischemic stroke; to examine the relationship of candidate genes polymorphisms with values of blood pressure, lipid metabolism and glucose depending on age and gender; based on the patterns of genes to appreciate significance of key-genes of genetic susceptibility to the ischemic stroke; to describe the influence of smoking – a behavioral risk factor of ischemic stroke, in the interaction between candidate genes.
Scientific novelty and originality: For the first time the comprehensive analysis of the genetic susceptibility to ischemic stroke in the population of the Republic of Moldova was held. It’s proved that AC haplotype, which includes alleles A rs10507391 locus and C allele rs9551963 locus of ALOX5AP gene is associated with increased levels of triglycerides and a decreased concentration of high density lipoprotein cholesterol with age and determine the increased risk for ischemic stroke. Based on the results was identified the gender heterogeneity of obtained associations, described gene interactions of studied polymorphic loci of candidate genes and characterized the impact of smoking on the type and power of intergenic interactions between loci rs9551963 ALOX5AP (A>C) and rs2910829 PDE4D (G>A).
The important scientific solved problem. It was detected the contribution of studied polymorphic gene variants F2, F5, GP1BA, PAI-1, ACE, ALOX5AP and PDE4D and some modifying risk factors (smoking, indices of lipid metabolism) in the susceptibility to ischemic stroke in the population of the Republic of Moldova. The theoretical significance. Presented results extend the knowledge of the genetic diversity and distribution of studied gene polymorphisms F2, F5, GP1BA, PAI-1, ACE, ALOX5AP and PDE4D in the population of the Republic of Moldova.
Applicative value of the thesis. The results of molecular-genetic analysis show a significant contribution to understanding the hereditary predisposition to ischemic stroke. The particularities of association of genetic markers with stroke based on gender can be used for the medico-genetic consultation. It’s recommended to identify the carriers of D allele of ACE gene for men and A allele of locus rs10507391 of ALOX5AP gene for women for early detection of individuals with high risk of cerebrovascular diseases and prenosological prevention.
The implementation of the scientific results. Results about the frequency distribution of the studied polymorphic variants of genes are used in the determination of cardiovascular risk in young population of Republic of Moldova, also its can be used in practical medicine and prevention of cerebrovascular disorders, the teaching of medical and clinical genetics, biochemistry, pathophysiology, internal medicine in the universities of medical and biological profile, as well as in courses of continuing medical education.