common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk

The genetic factors associated with carotid artery disease (CAAD) are not fully known. Because of its role in lipid metabolism, we hypothesized that common genetic variation in the very low density lipoprotein receptor (VLDLR) gene is associated with severe CAAD (>80% stenosis), body mass index (...

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Bibliographic Details
Published in:Journal of lipid research 2008-03, Vol.49 (3), p.588-596
Main Authors: Crawford, Dana C, Nord, Alex S, Badzioch, Michael D, Ranchalis, Jane, McKinstry, Laura A, Ahearn, Magdalena, Bertucci, Caterina, Shephard, Cynthia, Wong, Michelle, Rieder, Mark J, Schellenberg, Gerard D, Nickerson, Deborah A, Heagerty, Patrick J, Wijsman, Ellen M, Jarvik, Gail P
Format: Article
Language:English
Subjects:
5' Flanking Region
Apolipoproteins B
Apolipoproteins E - genetics
Body Mass Index
Carotid Artery Diseases - genetics
DNA Mutational Analysis
Genetic Predisposition to Disease
Genotype
Humans
Molecular Epidemiology
Polymorphism, Single Nucleotide
Receptors, LDL - genetics
Risk Factors
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Summary:The genetic factors associated with carotid artery disease (CAAD) are not fully known. Because of its role in lipid metabolism, we hypothesized that common genetic variation in the very low density lipoprotein receptor (VLDLR) gene is associated with severe CAAD (>80% stenosis), body mass index (BMI), and lipid traits in humans. VLDLR was resequenced for variation discovery in 92 subjects, and single nucleotide polymorphisms (tagSNPs) were chosen for genotyping in a larger cohort (n = 1,027). Of the 17 tagSNPs genotyped, one tagSNP (SNP 1226; rs1454626) located in the 5' flanking region of VLDLR was associated with CAAD, BMI, and LDL-associated apolipoprotein B (apoB). We also identified receptor-ligand genetic interactions between VLDLR 1226 and APOE genotype for predicting CAAD case status. These findings may further our understanding of VLDLR function, its ligand APOE, and ultimately the pathogenesis of CAAD in the general population.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.M700409-JLR200