Hitham A. Hypolipidemic effect of statins depending on polymorphism of CETP and eNOS gens in postmyocardial infarction patients.

Dissertation is devoted to studing hypolipidemics, endothelial protective and prognostic effects of statins in patients after myocardial infarction depending on Taq1B polymorphism of cholesterуl ester transfer protein (СЕТР) and Glu298Asp polymorphism of endothelial NO synthases gene (еNOS). It is established that prevalence of alleles and genotypes of polymorphic locus of Taq1B of СЕТР gene in postinfarction patients living in Kharkov region didn't differ from their frequency in healthy persons and European population of patients with ischemic heart disease. It is established that ischemic heart disease and myocardial infarction associate with allele Аsp and Asp/Asp genotype of polymorphic locus Glu298Asp of eNOS gene. Associations of Taq1B and Glu298Asp polymorphisms of СЕТР and eNOS genes with sex and some other risk factors of atherosclerosis and ischemic heart disease (obesity, smoking, heredity of cardiovascular diseases) are analyzed. Associations between Taq1B and Glu298Asp polymorphisms of СЕТР and eNOS genes are revealed. It is shown that genotype В2В2 of polymorphic locus Taq1B of СЕТР in postinfarction patients is characterized by more favorable lipid blood spectrum, but more endothelial dysfunction. Genotypes В1В1 and В1В2, on the contrary, are combined with more atherogenic lipid blood spectrum, but less endothelial dysfunction. Carriers of genotype Asp/Asp are characterized by the greatest degree endothelial dysfunction of epithelium among all postinfarction patients. It is shown that the result of statin treatment and the prognosis for the next months after myocardial infarction is defined by Taq1B and Glu298Asp polymorphism of СЕТР gene and eNOS gene. It is revealed that all patients with genotype В2В2 are tolerant to action of statins and have the worst prognosis in the first months after myocardial infarction. It is offered to consider В2В2 genotype in these patients as a marker of inefficiency of statin therapy and as a risk factor of the development of cardiovascular events.