Genetics
Heterozygous CETP-deficient HDL is remodeled toward more cholesteryl ester and less triglyceride but keeps normal antioxidative capacity (PLoS One 2012)
Original title: High-density lipoprotein (HDL) particle subpopulations in heterozygous cholesteryl ester transfer protein (CETP) deficiency: maintenance of antioxidative activity
Comparing HDL from 9 Caucasian heterozygous carriers of a CETP splice-site mutation (intron 7, causing premature truncation) with 9 age- and sex-matched normolipidemic family controls, researchers found HDL-C was 1.5-fold higher and CETP mass and activity were reduced by 31% and 38% respectively in carriers. Carrier HDL was enriched in cholesteryl ester (up to +19%, P less than 0.05) and depleted of triglyceride (up to -54%, P less than 0.01), giving up to a 2.5-fold lower triglyceride-to-cholesteryl-ester ratio, alongside a 22% increase in apoA-I content (P less than 0.05). Despite these compositional shifts, total HDL and small dense HDL3 from carriers protected LDL from oxidation as effectively as control HDL3 on a particle-mass basis, and circulating 8-isoprostane oxidative stress markers were similar between groups, showing HDL antioxidative function is preserved in heterozygous CETP deficiency.
Original abstract
Cholesteryl ester transfer protein (CETP) deficiency causes elevated high-density lipoprotein-cholesterol (HDL-C) levels; its impact on HDL functionality however remains elusive. We compared functional and compositional properties of HDL derived from 9 Caucasian heterozygous CETP mutation carriers (splice-site mutation in intron 7 resulting in premature truncation) with those of 9 age- and sex-matched normolipidemic family controls. As expected, HDL-C levels were increased 1.5-fold, and CETP mass and activity were decreased by -31% and -38% respectively, in carriers versus non-carriers. HDL particles from carriers were enriched in CE (up to +19%, p<0.05) and depleted of triglycerides (TG; up to -54%, p<0.01), resulting in a reduced TG/CE ratio (up to 2.5-fold, p<0.01). In parallel, the apoA-I content was increased in HDL from carriers (up to +22%, p<0.05). Both the total HDL fraction and small, dense HDL3 particles from CETP-deficient subjects displayed normal antioxidative activity by attenuating low-density lipoprotein oxidation with similar efficacy on a particle mass basis as compared to control HDL3. Consistent with these data, circulating levels of systemic biomarkers of oxidative stress (8-isoprostanes) were similar between the two groups. These findings support the contention that HDL functionality is maintained in heterozygous CETP deficiency despite modifications in lipid and protein composition.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.