PHARMACOLOGICAL APPROACHES FOR THE CORRECTION OF DEADAPTATION PROCESSES AND IHD PATIENTS WITH THE HELP OF GENETIC MARKERS

详细

全文:

Purpose of the work: the evaluation of hypolipidemic efficacy of the inhibitors of cholesterol synthesis by means of pharmacogenetic markers in the patients with an ischemic heart disease. Methods of the study: laboratory and instrumental study was conducted before the pharmacological interference in 4, 8, 24, and 48 weeks of hypolipidemic therapy: anthropometry, lipid spectrum of blood determination (total cholesterol, cholesterol of lipid proteids of high density, cholesterol of lipid proteids of low density, triglycerides, atherogenic index, conduction of daily screening of electrocardiography, veloergometry, supersonic scanning of brachiocephalic vessels, pharmacogenetic test - determination of carriage of allelic genes variants of CETP, NOS3. The study involved 120 men with ischemic heart disease (II functional class of exertional angina) with primary atherogenic hypercholesterinemias. Pharmacological correction with hypercholesterinemias was done with the use of IV generation statin - rosuvastatin. Results: we have studied polymorphous variants of genes involved into the regulation of lipid exchanges for the determination of differences in the rosuvastatin efficacy. We have implemented an evaluation of the influence of protein gen polymorphism - carrier of cholesterol ester (CETP) on the efficiency of patients’ treatment with rosuvastatin. Among the tested genetic models of phenotypic effects of CETP Taq1B of polymorphism at the level of lipid exchange indices, recessive model showed the most important gene-phenotypic interconnections. Homozygotes +279AA originally had less signified defects of lipid exchange indices - total cholesterol, cholesterol of lipoproteids of low density, triglycerides, atherogenic index, and a high basal level of cholesterol of lipoproteids of high density. Dynamic pattern of the cholesterol of high-density lipoproteids with rosuvastatin differed in patients with +279AA genotype in comparison with other genotypes of CETP. The domination of the level of lipoproteids cholesterol of high density in homozygotes +279AA were discovered on the 8th week and remained during the whole period of examination (+27.3%, P=0.004), in comparison with other genotypes carriers (+16.7%, P<0.001) by 48th week. Polymorph variants of NOS3 did not exhibit any impact on basal levels of lipoproteids in patients with IHD and atherogenic hypercholesterinemias excluding the content of triglycerides (P=0.054). Carriage of -786CC genotype led to the resistance of the statin used as a hypolipidemic drug. There were no differences in basal level of total cholesterol in patients with different genotype NOS3; in the course of pharmacological correction of the disturbances of a lipid exchange of homozygotes -786CC this index were high and insignificantly decreased by 48th week (-11.55%, P=0.524) in the settings of rosuvastatin treatment of patients with IHD and atherogenic hypercholesterinemias in comparison with genotype -786TT/TC, which had total cholesterol decreased to 39% (P<0.001). Conclusion: while implementing a monotherapy with rosuvastatin the carriage of +279AA genotype by the polymorphism CETP Taq1B was associated with the raise of cholesterol of high-density lipoproteid by 27% in comparison with +279GG/GA genotypes (16.7%) in patients with ischemic blood disease. Carriage of -786CC genotypes by polymorphism NOS3 -786T>C determined a low activity of rosuvastatin. The determination of genotypes by polymorphism CETP Taq1B and NOS3 -786TC marker can be used for an analyzed approach to the rosuvastatin prescription for the ischemic heart disease patients with isolated and combined hypercholesterinemia.