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

Abstract

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.

• Authors: Dana C Crawford, Alex S Nord, Michael D Badzioch, Jane Ranchalis, Laura A McKinstry, Magdalena Ahearn, Caterina Bertucci, Cynthia Shephard, Michelle Wong, Mark J Rieder, Gerard D Schellenberg, Deborah A Nickerson, Patrick J Heagerty, Ellen M Wijsman, Gail P Jarvik
• Journal: Journal of lipid research (J Lipid Res) Vol. 49 Issue 3 Pg. 588-96 (Mar 2008) ISSN: 0022-2275 [Print] United States
• PMID: 18056683 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Apolipoproteins B
• Apolipoproteins E
• Receptors, LDL
• VLDL receptor

Topics

• 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