(Circulation. 2000;101:2461.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Linkage of the Cholesteryl Ester Transfer Protein (CETP) Gene to LDL Particle Size
Use of a Novel Tetranucleotide Repeat Within the CETP Promoter
From the Centre for Genetics of Cardiovascular Disorders (P.J.T., C.M.T., J.M.P., S.E.H.), Department of Medicine, UCL Medical School, The Rayne Institute, University Street, London, UK; Department of Epidemiology (K.L.E., M.A.A.), School of Public Health and Community Medicine, University of Washington, Seattle, Wash; and School of Public Health (B.N.), Queensland University of Technology, Brisbane, Queensland, Australia.
Correspondence to Dr Philippa Talmud, Division of Cardiovascular Genetics, Dept of Medicine, University College London Medical School, Rayne Institute, University Street, London WC1E 6JJ, UK. E-mail p.talmud{at}ucl.ac.uk
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.
Key Words: lipoproteins • genetics • genes
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