Genetics
A novel CETP splice-site mutation causes isolated high HDL cholesterol in Caucasians, distinct from ordinary hyperalphalipoproteinemia (J Lipid Res 2007)
Original title: Cholesteryl ester transfer protein and hyperalphalipoproteinemia in Caucasians
This study investigated whether CETP contributes to HDL-cholesterol (HDL-C) levels in hyperalphalipoproteinemia (HALP, high HDL-C) in Caucasians, since hereditary CETP deficiency effects were largely undescribed outside Japanese populations, studying 95 unrelated Caucasian individuals with HALP. No correlation was found between CETP concentration or activity and HDL-C overall. Gene screening identified a novel heterozygous splice-site mutation in one individual; twenty-five heterozygous relatives for this mutation had reduced CETP concentration (-40%) and activity (-50%) and 35% higher HDL-C than family controls, presenting with isolated high HDL-C, unlike the typical high-HDL-C/low-triglyceride phenotype seen in the rest of the HALP cohort. The HDL-C increase in CETP-deficient heterozygotes was primarily due to increased apoA-I/A-II-containing HDL, contrasting with the other group. The authors conclude genetic CETP deficiency is rare in Caucasians and presents a phenotype distinct from HALP without CETP mutations.
Original abstract
It is unclear whether cholesteryl ester transfer protein (CETP) contributes to high density lipoprotein cholesterol (HDL-C) levels in hyperalphalipoproteinemia (HALP) in Caucasians. Moreover, even less is known about the effects of hereditary CETP deficiency in non-Japanese. We studied 95 unrelated Caucasian individuals with HALP. No correlations between CETP concentration or activity and HDL-C were identified. Screening for CETP gene defects led to the identification of heterozygosity for a novel splice site mutation in one individual. Twenty-five heterozygotes for this mutation showed reduced CETP concentration (-40%) and activity (-50%) and a 35% increase of HDL-C compared with family controls. The heterozygotes presented with an isolated high HDL-C, whereas the remaining subjects exhibited a typical high HDL-C/low-triglyceride phenotype. The increase of HDL-C in the CETP-deficient heterozygotes was primarily attributable to increased high density lipoprotein containing apolipoprotein A-I and A-II (LpAI:AII) levels, contrasting with an increase in both high density lipoprotein containing apolipoprotein A-I only and LpAI:AII in the other group. This study suggests the absence of a relationship between CETP and HDL-C levels in Caucasians with HALP. The data furthermore indicate that genetic CETP deficiency is rare among Caucasians and that this disorder presents with a phenotype that is different from that of subjects with HALP who have no mutation in the CETP gene.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.