Allelic variation in the gene encoding the cholesteryl ester transfer protein is associated with variation in the plasma concentrations of cholesteryl ester transfer protein

The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high density lipoproteins (HDL) to triglyceride-rich lipoproteins. Mutations that abolish CETP function are associated with very high levels of HDL cholesterol, but the effect of more common allelic variation at this locus is less clear. In this study, we have measured plasma CETP concentration and plasma HDL cholesterol concentrations in 694 individuals from 106 nuclear families. Robust sibling-pair methods indicated linkage between the CETP locus and inter-individual variation in plasma CETP concentrations. Allelic variation at the CETP locus accounted for 20% of the variation in plasma CETP concentration. No relation between allelic variation at the CETP locus and plasma HDL cholesterol levels was detected. These data indicate that polymorphism in the CETP gene confers variation in plasma CETP concentration. However, this degree of variation in CETP function is not systematically associated with variation in plasma HDL-C concentrations.