Genetics
CETP deficiency enlarges apoA-I lipoprotein particles and impairs their cholesterol-handling function (J Lipid Res 1995)
Original title: Structural and functional differences of subspecies of apoA-I-containing lipoprotein in patients with plasma cholesteryl ester transfer protein deficiency
In six patients with cholesteryl ester transfer protein (CETP) deficiency, both LpA-I and LpA-I/A-II apoA-I-containing lipoprotein subspecies increased, with LpA-I/A-II carrying sixty-five percent of plasma apoA-I and predominating. Both subspecies showed higher ratios of neutral to polar lipid and shifted to larger particle sizes than in normal subjects. Incubating patient LpA-I and LpA-I/A-II with CETP largely corrected these chemical and physical abnormalities. Cholesterol-reducing capacity from macrophage foam cells and cholesterol esterification rates in LpA-I, LpA-I/A-II, and whole plasma were all significantly lower than in normal controls. The findings indicate that the structure and function of apoA-I-containing HDL particles are severely affected by CETP deficiency.
Original abstract
ApoA-I-containing lipoproteins exist in plasma in two main forms: one contains only apoA-I (LpA-I) while the other contains both apoA-I and apoA-II (LpA-I/A-II). We characterized structural and functional changes of these lipoproteins in six patients with cholesteryl ester transfer protein (CETP) deficiency. In these patients, the amount of LpA-I and LpA-I/A-II had increased significantly. Sixty-five percent of plasma apoA-I was associated with LpA-I/A-II, which indicated that LpA-I/A-II was predominant. The chemical composition of both LpA-I and LpA-I/A-II was characterized by increased ratios of neutral to polar lipid, compared with findings in normal subjects. Particle sizes of these lipoproteins shifted to larger diameter ranges, as compared to the size seen in normal subjects. Incubation of patients' LpA-I and LpA-I/A-II with CETP markedly corrected the chemical and physical abnormalities in these lipoproteins. Cholesterol-reducing capacities of these lipoproteins from macrophage foam cells were significantly lower than in normal controls. Cholesterol esterification rates in LpA-I, LpA-I/A-II, and plasma were significantly lower in patients than in normal controls. We propose that the structure and function of LpA-I and LpA-I/A-II are severely affected in the presence of CETP deficiency.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.