Submitted on September 11, 2007
Revised on November 30, 2007
Accepted on December 2, 2007
A common VLDLR polymorphism interacts with APOE in the prediction of carotid artery disease
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, and Gail P. Jarvik
Division of Medical Genetics, University of Washington Medical Center, Seattle, WA 98195-7720
Corresponding Author: pair{at}u.washington.edu
The genetic factors associated with carotid artery disease (CAAD) are not fully known. Due to its role in lipid metabolism, we hypothesized that common genetic variation in the very low density lipoprotein receptor (VLDLR) gene is associated with severe carotid artery disease (CAAD; >80% stenosis), body mass index (BMI), and lipid traits in humans. VLDLR was re-sequenced for variation discovery in 92 subjects, and tagSNPs were chosen for genotyping in a larger cohort (n=1027). 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 (LDL B). 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.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
