HDL biology
Review makes CETP deficiency the central explanation for hyperalphalipoproteinemia and its paradoxical coronary risk (Atherosclerosis 2000)
Original title: Molecular mechanisms, lipoprotein abnormalities and atherogenicity of hyperalphalipoproteinemia
This review identifies plasma CETP deficiency as the most important and frequent cause of hyperalphalipoproteinemia in Asian populations. CETP normally transfers cholesteryl ester from HDL to apolipoprotein B-containing lipoproteins as part of reverse cholesterol transport, and its deficiency alters the concentration, composition, and function of both HDL and LDL. In vitro evidence shows the large cholesteryl-ester-rich HDL particles seen in CETP deficiency are defective in cholesterol efflux, paralleling accelerated atherosclerosis in HDL-raised but SR-BI knockout mice. Epidemiological studies in Japanese-Americans and in the Omagari area, where the CETP gene's intron 14 splicing defect is markedly frequent, found increased coronary atherosclerosis among CETP-deficient patients, framing CETP deficiency as a state of impaired reverse cholesterol transport rather than simple cardioprotection.
Original abstract
Hyperalphalipoproteinemia (HALP) is caused by a variety of genetic and environmental factors. Among these, plasma cholesteryl ester transfer protein (CETP) deficiency is the most important and frequent cause of HALP in the Asian populations. CETP facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein (apo) B-containing lipoproteins, and is a key protein in the reverse cholesterol transport system. The deficiency of CETP causes various abnormalities in the concentration, composition, and function of both HDL and low density lipoprotein (LDL). The significance of CETP in terms of atherosclerosis had been controversial. However, the in vitro evidence showed large CE-rich HDL particles in CETP deficiency are defective in cholesterol efflux. Similarly, scavenger receptor BI (SR-BI) knockout mice show a marked increase in HDL-cholesterol but accelerated atherosclerosis in atherosclerosis-susceptible mice. Recent epidemiological studies in Japanese-Americans and in Omagari area where HALP subjects with the intron 14 splicing defect of CETP gene are markedly frequent, have demonstrated an increased incidence of coronary atherosclerosis in CETP-deficient patients. Thus, CETP deficiency is a state of impaired reverse cholesterol transport which may possibly lead to the development of atherosclerosis. The current review will focus on the molecular mechanisms and atherogenicity of HALP, especially CETP deficiency.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.