Genetic Polymorphisms and Activity of Cholesterol Ester Transfer Protein (CETP): Should We Be Measuring Them?

Abstract

Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that mediates the transfer of cholesteryl ester from high density lipoproteins (HDL) to triglyceride-rich lipoproteins in exchange for triglycerides. Several approaches are currently being used in research laboratories to measure its activity and/or mass. However, these assays are not standardized and it is not possible to compare data from different laboratories. Also, we lack enough information to assess the value of this variable as a coronary heart disease (CHD) predictor. Several genetic variants at CETP locus have been identified and they have been generally associated with increased HDL-cholesterol concentrations. However, there is no consensus about the association of this CETP-related increase in HDL-cholesterol and protection against CHD. Nevertheless, the most recent evidence from the common CETP-TaqI-B polymorphism shows that the lower CETP activity associated with the presence of this polymorphism decreases CHD risk in men. Based on this and previous evidence, there has been an interest in the development of CETP inhibitors as a tool to increase HDL-cholesterol, thus reducing CHD risk. However, it should be noted that the evidence about the cardioprotective role of these drugs is not yet available.