Linkage of the Cholesteryl Ester Transfer Protein ( CETP ) Gene to LDL Particle Size
- 30 May 2000
- journal article
- other
- Published by Wolters Kluwer Health in Circulation
- Vol. 101 (21) , 2461-2466
- https://doi.org/10.1161/01.cir.101.21.2461
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 P 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 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.Keywords
This publication has 21 references indexed in Scilit:
- Cholesteryl ester transfer protein gene effect on CETP activity and plasma high‐density lipoprotein in European populationsEuropean Journal of Clinical Investigation, 1999
- In vitro production of β-very low density lipoproteins and small, dense low density lipoproteins in mildly hypertriglyceridemic plasma: role of activities of lecithin:cholester acyltransferase, cholesterylester transfer proteins and lipoprotein lipaseAtherosclerosis, 1998
- LDL Size Distribution in Relation to Insulin Sensitivity and Lipoprotein Pattern in Young and Healthy SubjectsDiabetes Care, 1998
- Families with Familial Combined Hyperlipidemia and Families Enriched for Coronary Artery Disease Share Genetic Determinants for the Atherogenic Lipoprotein PhenotypeAmerican Journal of Human Genetics, 1998
- Evidence That Cholesteryl Ester Transfer Protein-mediated Reductions in Reconstituted High Density Lipoprotein Size Involve Particle FusionJournal of Biological Chemistry, 1997
- Human Cholesteryl Ester Transfer Protein Gene Proximal Promoter Contains Dietary Cholesterol Positive Responsive Elements and Mediates Expression in Small Intestine and Periphery While Predominant Liver and Spleen Expression Is Controlled by 5′-distal SequencesPublished by Elsevier ,1996
- Absence of cholesteryl ester transfer protein‐mediated cholesteryl ester mass transfer from high‐density lipoprotein to low‐density lipoprotein particles is a major feature of combined hyperlipidaemiaEuropean Journal of Clinical Investigation, 1996
- The NHLBI Twin Study: heritability of apolipoprotein A-I, B, and low density lipoprotein subclasses and concordance for lipoprotein(a)Atherosclerosis, 1991
- The interaction of cholesteryl ester transfer protein and unesterified fatty acids promotes a reduction in the particle size of high-density lipoproteinsBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1990
- Cholesteryl ester exchange protein in human plasma isolation and characterizationBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1978