LIPID, CARDIOVASCULAR AND PHARMACOGENETIC EFFECTS OF A COMMON VARIANT IN THE АВСА1 GENE (rs2230806)
P.P. Malyshev1, G.P. Smirnov2, D.N. Nozadze1, I.V. Sergienko1
1National Medical Research Center of Cardiology of Minzdrav of Russia, 121552, Moscow, 3rd Cherepkovskaya str., 15A
2City Polyclinic № 212 of the Moscow Healthcare Department, 119620, Moscow, Solntsevsky av., 11A
Keywords: ATP-binding cassette transporter A1, coronary heart disease, ABCA1 gene polymorphism, statins, R219K, rs2230806
Abstract
ATP-binding cassette transporters (ABC) are a family of proteins that function as transmembrane carriers of molecules using adenosine triphosphate (ATP) hydrolysis as an energy source. ABCA1 is a protein that functions as a «cholesterol pump» in the removal of lipids from the cell and transfersthe cholesterol and phospholipids from the cell membrane to apolipoproteins for the subsequent formation of nascent high-density lipoproteins (HDL). The most common and one of the most studied is the nonsynonymous allelic variant rs2230806; however, the effects of this genetic polymorphism on atherosclerosis and lipid profile till now remain debatable. The phenotypic effects of this variant are opposite to those observed in the ABCA1 mutationheterozygous carriers, suggesting that this genetic variant is associated with increased ABCA1 function and reverse cholesterol transport. Meta-analyses confirmed the association of rs2230806 polymorphism with higher levels of HDL cholesterol and lower levels of TG and LDL cholesterol in the general population, which could mediate a decrease in the risk of coronary heart disease in allelic carriers. It is known that the relationship of rs2230806 variant with HDL levels and coronary heart disease is more stable and consistent in Asian populations than in European ones. Single pharmacogenetic studies show no effect of rs2230806 ABCA1 on the main lipotropic effect of statins, reduction of LDL-C, but indicate a positive reaction of HDL in one study. In practice, the detection of this genetic polymorphism, along with other ABCA1 allelic variants, can be used for screening of persons at higher risk of coronary heart disease with the early preventive measures in carriers of risk alleles.
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