[The effect of ABCA1 rs2230806 common gene variant on plasma lipid levels in patients with dyslipidemia.]

The aim of this work was to assess the relationship of rs2230806 SNP of ABCA1 with lipid profile in patients with severe dyslipidemia. The study included 363 patients (42.8% of males), the average age was 48.7 years, 35.5% of patients received hypolipidemic drugs (mainly statins). Quantitative determination of total cholesterol (ТС) and triglycerides (TG) in fasting serum was carried out by a unified enzymatic method, and high density lipoproteins (HDL) - by a direct homogeneous method. Genotype according to the rs2230806 position in the ABCA1 gene was determined by polymerase chain reaction (PCR) «in real time¼ using adjacent samples and melting reaction products after PCR. The frequencies of alleles and genotypes of variant rs2230806 of ABCA1 gene in patients with dyslipidemia did not differ from those in the control group of healthy individuals (athletes). The levels of plasma lipids - TC, TG and HDL cholesterol, on average, in patients with dyslipidemia were 7.8±3,4, 3,4±6,5 and 1.29±0.4 mmol/l, respectively. Compared to different genotypes, the plasma lipid concentrations did not differ significantly, but the analysis of different inheritance models of the allelic variant studied showed a significant association with the level of TG in the additive model, in which each minor allele (a) further enhanced the effect on the level of plasma TG at 1.02 mmol/l (p=0.044). The results of this study demonstrate the effect of a common variant rs2230806 of the ABCA1 gene on the plasma TG level in patients with severe dyslipidemia.

[The positional isomers of palmitic and oleic triglycerides, lipolysis, conformation of apoB-100, formation of apoE/B-100 ligand and absorption of lipoproteins of very low density by insulin-dependent cells under action of statins.]

The study was carried out to trace back quantitative alterations of positional isomers, oleic and palmitic triglycerides and individual fatty acids in blood serum. After two weeks of taking of Simvastatin (40, 80 mg), analysis of blood serum established decreasing of content of Рhosphatidylcholine and more reliable decreasing of amount of non-etherized alcohol cholesterol. No alterations of content of particular fatty acids were detected. In apoB-100, Рhosphatidylcholine and non-etherized alcohol cholesterol form polar mono-layer; it covers mass of oleic and palmitic triglycerides that was bound by apoB-100 in oleic and palmitic lipoproteins of very low density disturbing bio-availability of substrate (oleic and palmitic triglycerides) for post-heparin lipase. This very pool of non-etherized alcohol cholesterol is inhibited by statins activating lipolysis in oleic and palmitic lipoproteins of very low density. In blood was detected amount of palmitic positional isomersin oleic and palmitic triglycerides (palmitoyl-palmitoyl-palmitate and palmitol-palmitoyl-oleate) and oleic positional isomers (oleyl-oleyl-palmitate and oleyl-oleyl-oleate). The significant difference was marked in content of positional isomers both of oleyl-oleyl-oleate and oleyl-oleyl-palmitate; their content is less in blood of patients of experimental group as compared with healthy people. In case of treatment with Simvastatin (40 mg) the level of palmitic positional isomers and palmitol-palmitoyloleate is decreased. In case of treatment with Simvastatin (80 mg) significant decreasing of positional isomers-palmitolpalmitoyl-oleate and oleyl-oleyl-palmitate as compared with data before treatment. The detection of content of positional isomers triglycerides permits: a) to characterize disorders of metabolism of palmitic fatty acid, oleic fatty acid, oleic and palmitic triglycerides and oleic and palmitic lipoproteins of very low density of the same name; b) to form individual diet therapy; c) to obtain objective information concerning compliance of prescribed recommendations b y patient. The basis of primary prevention of atherosclerosis and atheromatosis is in decreasing up to physiological level in food the content of longchained saturated fatty acids mainly palmitic acid.

[THE EFFECT OF SATINS: ACTIVATION OF LIPOLYSIS AND ABSORPTION BY INSULIN-DEPENDED CELLS LIPOPROTEINS OF VERY LOW DENSITY, INCREASING OF BIO-AVAILABILITY OF POLYENOIC FATTY ACIDS AND DECREASING OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

The Russian cardiologic R&D production complex of Minzdrav of Russia, 121552 Moscow, Russia The statins are synthetic xenobiotics alien to animal cells. They are unlikely capable to manifest pleiotropic effect. It is feasible to evaluate effect of statins by stages: a) initially a specific inhibition of synthesis of cholesterol alcohol; b) further indirect activation of hydrolysis of triglycerides in lipoproteins of very low density; c) nonspecific activation of cells' receptor absorption of palmitic and oleic lipoproteins of very low density and then d) linoleic and linolenic lipoproteins of low density with all polyenoic fatty acids. On balance, statins activate absorption ofpolyenoic fatty acids by cells. Just they manifest physiological, specific pleiotropic effect. The statins inhibit synthesis of pool of cholesterol alcohol-lipoproteins of very low density condensed between phosphatidylcholines in polar mono-layer phosphatidylcholines+cholesterol alcohol on surface oftriglycerides. The low permeability of mono-layer separates substrate-triglycerides in lipoproteins of very low density and post-heparin lipoprotein lipase in hydrophilic blood plasma. The higher is ratio cholesterol alcohol/phosphatidylcholines in mono-layer of lipoproteins of very low density the slower is lipolysis, formation of ligand lipoproteins of very low density and their absorption by cells under apoB-100-endocytosis. The statins normalize hyperlipemia by force of a) activation of absorption oflipoproteins of very low density by insulin-depended cells and b) activation of absorption of lipoproteins of low density by all cells, increasing of bio-availability of polyenoic fatty acids, activation of apoB-100-endocytosis. The limitation in food of content of palmitic saturated fatty acid and increasing of content of ω-3 polyenoic fatty acids improve "bio-availability" of polyenoic fatty acids and their absorption by cells and also decreases cholesterol alcohol/phosphatidylcholines and biological pleiotropic effect of essential polyenoic fatty acids. According our opinion, atherosclerosis is intracellular deficiency of polyenoic fatty acids. The value of cholesterol alcohol-lipoproteins of low density is equimolar to content of lipoproteins of low density in blood which under low bio-availability can't to absorb cells byforce of apoB-100-endocytosis.