Genetics
New CETP promoter repeat marker links the gene to LDL particle size, triglycerides, and apoB in twins (Circulation 2000)
Original title: Linkage of the cholesteryl ester transfer protein (CETP) gene to LDL particle size: use of a novel tetranucleotide repeat within the CETP promoter
To investigate genetic determinants of the atherogenic lipoprotein phenotype (small dense LDL, elevated triglycerides, low HDL), researchers identified a novel tetranucleotide repeat (324-464 bp, heterozygosity index 0.74) within the CETP gene promoter and used it for quantitative sib-pair linkage analysis in 119 female dizygotic twins. Significant linkage was found between this CETP marker and LDL particle size (P<0.001), plasma triglycerides (P<0.005), and plasma apoB (P=0.02). The tetranucleotide repeat distribution was bimodal, with the 'short' alleles strongly associated with the B2 allele of the CETP TaqIB polymorphism (P<0.001). This linkage of the CETP gene to LDL particle size adds CETP to the list of candidate genes supporting multigenic determination of LDL size heterogeneity, though whether the promoter repeat itself is functional remains unresolved.
Original abstract
Background: A preponderance of small, dense LDL particles, elevated levels of plasma triglycerides (TG), and low levels of HDL characterize the atherogenic lipoprotein phenotype, which is associated with increased coronary artery disease (CAD) risk. Genetic and environmental factors influence LDL size, cholesteryl ester transfer protein (CETP) being one of the candidate genes. CETP mediates the transfer of cholesteryl ester from HDL to apolipoprotein (apo) B-containing lipoproteins in exchange for TG, promoting reverse cholesterol transfer and remodeling of lipoprotein particles.
Methods And Results: We have identified a tetranucleotide repeat (fragment sizes from 324 to 464 bp; heterozygosity index = 0.74) within the CETP promoter and used it in quantitative sib-pair linkage analysis in 119 female dizygotic (DZ) twins. Linkage was found to LDL size (P<0.001), TG (P<0.005), and plasma apoB (P = 0.02). The distribution of the tetranucleotide repeats was bimodal, and there was strong allelic association of the "short" alleles with the B2 allele of CETP TaqIB polymorphic site (P<0.001).
Conclusions: This report of linkage of the CETP gene to LDL particle size adds to the list of candidate genes linked to LDL size, supporting the hypothesis of multigenic determination of LDL size heterogeneity. Whether this promoter variation is itself functional or is a marker for a functional site in the CETP gene remains to be determined.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.