ASSESSMENT OF THE EFFECT OF RS2230806 ALLELIC VARIANT IN THE ABCA1 GENE ON THE LIPID-LOWERING EFFECTS OF ATORVASTATIN IN PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
G.P. Smirnov1, T.A. Rozhkova1, M.Yu. Zubareva1, Yu.A. Shuvalova1, D.V. Rebrikov2,3, A.I. Kaminny1, V.N. Titov1, V.V. Kukharchuk1, P.P. Malyshev1
1National Medical Research Center of Cardiology of Minzdrav of Russia, 121552, Moscow, 3rd Cherepkovskaya str., 15A
2Pirogov Russian National Research Medical University of Minzdrav of Russia, 117997, Moscow, Ostrovityanova str., 1
3Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology of Minzdrav of Russia, 117997, Moscow, Academician Oparin str., 4
Keywords: аторвастатин, АТФ-связывающий кассетный транспортер А1, полиморфизм гена АВСА1, семейная гиперхолестеринемия, R219K, rs2230806, ABCA1 gene polymorphism, atorvastatin, ATP-binding cassette transporter A1, familial hypercholesterolemia, R219K, rs2230806
Abstract
Objective: to evaluate the effect of rs2230806 variant in the ABCA1 gene on lipid and apolipoprotein (apo)A-I and apoB levels after the atorvastatin treatment in patients with heterozygous familial hypercholesterolemia (FH). Material and methods. The study included 83 patients with FH according to the British clinical SBR-criteria of the disease, all patients received atorvastatin at a dose of 40 mg/day for 3 months.Genotypingthe rs2230806 polymorphism was determined by «real time» polymerase chain reaction (PCR) using adjacent samples and melting reaction products after PCR. Total cholesterol (TC) and triglycerides (TG) were determined by a unified enzymatic method, high - density lipoproteins (HDL) and low - density lipoproteins (LDL) - by a direct homogeneous method, apoproteins - by immunoturbidimetric method. Results. Carriers of allelic variant were 52.9 % of patients (with one allele in 31.4 %, with two in 21.4 %). We revealed a difference in the change from the initial values of TC (-40.2 % vs. -34.4 %; p = 0.041), LDL (-50.8 % vs. -44 %; p = 0.041) and apoB (-48 % vs. -38.3 %; p = 0.02) with greater response to atorvastatin in homozygous carriers (genotype A/A) compared with heterozygous (genotype G/A) ones. The selective analysis depending on the sex and genotype rs2230806 among male carriers of allelic variant revealed a significant increase in the levels of HDL and apoAI by 10.6 % and 15.5 %, respectively, while in patients without polymorphism these lipid parameters decreased (by 3.8 % and 3.9 %, respectively). Conclusion. The variant rs2230806 in the ABCA1 gene was associated with a significant lipid-lowering effect of atorvastatin, and also increased the levels of apoA-containing plasma lipoproteins in male patients with FH.
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