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

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.

R219K, rs2230806, ABCA1 gene polymorphism, atorvastatin, ATP-binding cassette transporter A1, familial hypercholesterolemia, R219K, rs2230806

1. Goldstein J.L., Hobbs H.H., Brown M.S. Familial hypercholesterolemia // The metabolic basis of in heriteddisease / еds. C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle. N.Y.: McGraw-Hill, 1996. Vol. 120. P. 2863-2913.

2. Mytilinaiou M., Kyrou I., Khan M. et al. Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management // Front. Pharmacol. 2018. Vol. 9. P. 707.

3. Li J., Wang L.-F., Li Z.Q., Pan W. Effect of R219K polymorphism of the ABCA1 gene on the lipid-lowering effect of pravastatin in Chinese patients with coronary heart disease // Clin. Exp. Pharmacol. Physiol. 2009. Vol. 36, N 5-6. P. 567-570.

4. Akao H., Polisecki E., Schaefer E.J. et al. ABCA1 Gene Variation and Heart Disease Risk Reduction in the Elderly during Pravastatin Treatment // Atherosclerosis. 2014. Vol. 235, N 1. P. 176-181.

5. Scientific Steering Committee on behalf of the Simon Broome Register Group. Risk of fatal coronary heart disease in familial hypercholesterolaemia // BMJ. 1991. Vol. 303. P. 893-896.

6. Ребриков Д.В., Саматов Г.А., Трофимов Д.Ю. ПЦР в реальном времени. М.: BINOM, 2009. 215 с.

7. Clee S.M., Zwinderman A.H., Engert J.C. et al. Common genetic variation in ABCA1 isassociated with altered lipoprotein levels and a modified risk for coronary artery disease // Circulation. 2001. Vol. 103. P. 1198-1205.

8. Ma X.Y., Liu J.P., Song Z.Y. Associations of the ATP-binding cassette transporter A1 R219K polymorphism with HDL-C level and coronary artery disease risk: A meta-analysis // Atherosclerosis. 2011. Vol. 215. P. 428-434.

9. Yin Y.W., Li J.C., Gao D. et al. Influence of ATP-binding cassette transporter 1 R219K and M883I polymorphisms on development of atherosclerosis: a meta-analysis of 58 studies // PLoS One. 2014. Vol. 9, N 1. P. e86480.

10. Cenarro A., Artieda M., Castillo S. et al. A common variant in the ABCA1 gene is associated with a lower risk for premature coronary heart disease in familial hypercholesterolaemia // J. Med. Genet. 2003. Vol. 40, N 3. P. 163-168.

11. Versmissen J., Oosterveer D.M., Yazdanpanah M. et al. A frequent variant in the ABCA1 gene is associated with increased coronary heart disease risk and a better response to statin treatment in familial hypercholesterolemia patients // Eur. Heart J. 2011. Vol. 32, N 4. P. 469-475.

12. Villard E.F., EI Khoury P., Frisdal E.et al. Genetic determination of plasma cholesterol efflux capacity is gender-specific and independent of HDL-cholesterol levels // Arterioscler. Thromb. Vasc. Biol. 2013. Vol. 33, N 4. P. 822-828.