ApoE-rich HDL is a better CETP substrate than apoA-II-containing HDL, three CETP-deficiency genotypes reveal (J Lipid Res 1997)

High density lipoprotein (HDL) with and without apolipoprotein (apo) E was quantified and characterized in subjects with three genotypes of cholesteryl ester transfer protein (CETP) deficiency: the nonsense mutation in intron 14 (10 homozygotes and 5 heterozygotes); the missense mutation in the exon 15 (3 homozygotes and 9 heterozygotes); and the Int14A/D442G in 6 compound heterozygotes. ApoE-poor and apoE-rich HDL-cholesterol levels were elevated significantly in all genotypic groups with the decrease in CETP activity, indicating that both types of HDL-cholesterol can be a substrate for CETP. However, an unchanged or only slightly increased serum apoA-II level in each genotype indicated that the HDL particles with apoA-II are relatively resistant to CETP-mediated lipid transfer. Serum apoE-rich HDL level was considerably higher in the Int14A homozygotes than in the compound heterozygotes, in spite of similar apoE-poor HDL-cholesterol levels, which may indicate that apoE-rich HDL is a better substrate for CETP than apoE-poor HDL. Although the apoE-rich and apoE-poor HDL subclasses were similar in the accumulation of cholesteryl ester and depletion of triglyceride, the accumulation of free cholesterol was unique to apoE-rich HDL, indicating inhibited cholesterol esterification on this lipoprotein. Clinical laboratories should be aware of the discrepancy in HDL-cholesterol measurements that comes from the different recoveries of apoE-rich HDL using commercial reagents. In conclusion, CETP deficiency causes considerable quantitative and compositional changes in HDL subclasses, reflecting a significant physiological role for CETP in HDL metabolism.