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Publication Detail
Linkage of the cholesteryl ester transfer protein (CETP) gene to LDL particle size: use of a novel tetranucleotide repeat within the CETP promoter
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Talmud PJ, Edwards KL, Turner CM, Newman B, Palmen JM, Humphries SE, Austin MA
  • Publication date:
    30/05/2000
  • Pagination:
    2461, 2466
  • Journal:
    Circulation
  • Volume:
    101
  • Issue:
    21
  • Print ISSN:
    0009-7322
  • Keywords:
    Allele, Alleles, analysis, Apolipoproteins, Apolipoproteins B, Arteries, artery, Association, Blood, Candidate Gene, cardiovascular, Carrier Proteins, chemistry, Cholesterol, Cholesterol Esters, coronary artery, CORONARY ARTERY DISEASE, disease, DISORDER, Disorders, distribution, environmental, factors, Female, functional, GENE, Genes, genetic, genetics, glycoprotein, Glycoproteins, Heterogeneity, Heterozygosity, Heterozygote, Id, LDL, LEVEL, Linkage, Linkage (Genetics), Lipoproteins, Lipoproteins, HDL, Lipoproteins, LDL, medicine, Methods, Microsatellite Repeats, Middle Age, novel, particle, Particle Size, Particles, Phenotype, plasma, Promoter Regions (Genetics), PROTEIN, Proteins, Risk, SITE, size, STATE, STATES, Support, Non-U.S.Gov't, Support, U.S.Gov't, P.H.S., transfer proteins, triglyceride, Triglycerides, Twins, UCL, UK, United States
  • Addresses:
    Centre for Genetics of Cardiovascular Disorders, Department of Medicine, UCL Medical School, The Rayne Institute, University Street, London, UK. p.talmud@ucl.ac.uk
  • Notes:
    UI - 20292970 LA - eng RN - 0 (Apolipoproteins) RN - 0 (Apolipoproteins B) RN - 0 (Carrier Proteins) RN - 0 (Cholesterol Esters) RN - 0 (Glycoproteins) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (Triglycerides) RN - 0 (cholesterol ester transfer proteins) PT - Journal Article ID - HL41830/HL/NHLBI ID - HL46880/HL/NHLBI DA - 20000626 IS - 1524-4539 SB - AIM SB - IM CY - UNITED STATES JC - DAW
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
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