A 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 (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.
Crawford
Dana C
DC
Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA.
Nord
Alex S
AS
Badzioch
Michael D
MD
Ranchalis
Jane
J
McKinstry
Laura A
LA
Ahearn
Magdalena
M
Bertucci
Caterina
C
Shephard
Cynthia
C
Wong
Michelle
M
Rieder
Mark J
MJ
Schellenberg
Gerard D
GD
Nickerson
Deborah A
DA
Heagerty
Patrick J
PJ
Wijsman
Ellen M
EM
Jarvik
Gail P
GP
D024506:5' Flanking Region; D001055:Apolipoproteins B; D001057:Apolipoproteins E / Q000235:genetics*; D015992:Body Mass Index; D002340:Carotid Artery Diseases / Q000235:genetics*; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D017720:Molecular Epidemiology; D020641:Polymorphism, Single Nucleotide; D011973:Receptors, LDL / Q000235:genetics*; D012307:Risk Factors
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D011973:Receptors, LDL; C036053:VLDL receptor