Genetics
CETP deficiency yields abnormally large, cholesterol-rich apoA-I lipoprotein particles that bind but internalize poorly (Eur J Biochem 1995)
Original title: Characterization of high-density apolipoprotein particles A-I and A-I:A-II isolated from humans with cholesteryl ester transfer protein deficiency
ApoA-I-containing lipoprotein particles, LpA-I and LpA-I:A-II, were isolated from three subjects with homozygous CETP deficiency and compared with normolipidemic controls. Plasma apoA-I concentrations in both particle classes were significantly elevated in CETP-deficient subjects, and both particle types were larger and carried more cholesteryl ester per particle, including unusually large subpopulations with Stokes diameters of 13.8 nm and 12.6 nm not seen in normal subjects. The molar ratio of apoA-I to apoA-II in LpA-I:A-II was higher in CETP deficiency (mean 2.4) than controls (mean 1.4), apoE was concentrated in LpA-I:A-II, and a pre-beta-migrating LpA-I subclass was increased. Both particle types from CETP-deficient subjects bound HepG2 cells with higher affinity but lower capacity and were internalized less than control particles, showing CETP absence reshapes the plasma concentration, size, composition, and cellular handling of both major apoA-I lipoprotein classes.
Original abstract
The cholesteryl ester transfer protein (CETP) plays an important role in metabolism of high-density lipoprotein and reverse cholesterol transport in humans. The two major classes of high-density lipoprotein particles are those containing apolipoprotein A-I (LpA-I) and those containing both apoA-I and apoA-II (LpA-I:A-II). We isolated and characterized the apoA-I-containing lipoprotein particles from three subjects with homozygous CETP deficiency (CETP-D) and compared the results with those from normolipidemic control subjects. Plasma concentrations of apoA-I in both LpA-I and LpA-I:A-II were significantly elevated in CETP-D subjects. Both LpA-I and LpA-I:A-II from these subjects were larger and contained more cholesteryl ester per particle than control particles. In CETP-D, subpopulations of LpA-I and LpA-I:A-II with an unusually large size (Stokes diameters 13.8 nm and 12.6 nm, respectively) not detected in normal subjects were isolated. The molar ratio of apoA-I to apoA-II in LpA-I:A-II isolated from CETP-D subjects was higher (mean 2.4) than those of controls (mean 1.4). ApoE was primarily associated with LpA-I:A-II in CETP-D subjects. A subclass of LpA-I with pre-beta migration on agarose electrophoresis was increased in CETP-D subjects. Both LpA-I and LpA-I:A-II from CETP-D subjects bound with higher affinity but less capacity to HepG2 cells compared with control particles, and were internalized to a lesser extent than control particles. These data suggest that the absence of CETP in humans significantly affects the plasma concentration, size, composition, and cellular interaction of both major classes of apoA-I-containing lipoprotein particles.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.