Genetics
A novel CETP promoter deletion causing CETP deficiency does not impair HDL function in reverse cholesterol transport (Atherosclerosis 2011)
Original title: CETP deficiency due to a novel mutation in the CETP gene promoter and its effect on cholesterol efflux and selective uptake into hepatocytes
This study identified the genetic variant responsible for high HDL-cholesterol and low CETP activity in a proband, and tested whether the resulting HDL was dysfunctional in the reverse cholesterol transport (RCT) pathway, by sequencing the CETP gene, assessing promoter activity, and performing cholesterol efflux and hepatic cholesteryl ester delivery studies using HDL from the proband. The proband was a compound heterozygote for the known D459G variant and a novel 18-base-pair deletion mutation in the CETP promoter, which markedly reduced transcriptional activity in HepG2 cells. HDL2 from this CETP-deficient subject showed increased SR-BI-mediated cholesterol efflux, while cholesteryl ester delivery into hepatocytes was maintained. The authors conclude this novel CETP promoter deletion is associated with high HDL-cholesterol and reduced promoter activity, but the resulting HDL was not dysfunctional in mediating the two main steps of RCT tested in vitro.
Original abstract
Objectives: To identify the genetic variant in the CETP gene of the proband with high HDL-C and low CETP activity and to investigate whether HDL from the CETP-deficient subject was dysfunctional in the reverse cholesterol transport (RCT) pathway.
Methods: We sequenced the CETP gene and assessed its promoter activity. Cholesterol efflux and hepatic cholesteryl ester delivery studies were also performed using HDL from the proband.
Results: A proband was a compound heterozygote for a known D459G variant and a novel 18-bp deletion mutation in the CETP promoter. This promoter mutation markedly reduced the transcriptional activity in HepG2 cells. HDL2 from this subject increased SR-BI-mediated cholesterol efflux, whereas cholesteryl ester delivery into hepatocytes was maintained.
Conclusion: A novel deletion mutation in the CETP promoter is associated with high HDL-C and decreased promoter activity. HDL from this CETP-deficient subject was not dysfunctional in mediating two main steps of RCT assessed in vitro.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.