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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 588-596 |
| Number of pages | 9 |
| Journal | Journal of Lipid Research |
| Volume | 49 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2008 |
| Externally published | Yes |
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Keywords
- Apolipoprotein E
- Body mass index
- Triglycerides
- Very low density lipoprotein receptor
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology
Cite this
A common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk. / Crawford, Dana C.; Nord, Alexander; 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.
In: Journal of Lipid Research, Vol. 49, No. 3, 01.03.2008, p. 588-596.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk
AU - Crawford, Dana C.
AU - Nord, Alexander
AU - Badzioch, Michael D.
AU - Ranchalis, Jane
AU - McKinstry, Laura A.
AU - Ahearn, Magdalena
AU - Bertucci, Caterina
AU - Shephard, Cynthia
AU - Wong, Michelle
AU - Rieder, Mark J.
AU - Schellenberg, Gerard D.
AU - Nickerson, Deborah A.
AU - Heagerty, Patrick J.
AU - Wijsman, Ellen M.
AU - Jarvik, Gail P.
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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.
AB - 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.
KW - Apolipoprotein E
KW - Body mass index
KW - Triglycerides
KW - Very low density lipoprotein receptor
UR - http://www.scopus.com/inward/record.url?scp=42949136636&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42949136636&partnerID=8YFLogxK
U2 - 10.1194/jlr.M700409-JLR200
DO - 10.1194/jlr.M700409-JLR200
M3 - Article
C2 - 18056683
AN - SCOPUS:42949136636
VL - 49
SP - 588
EP - 596
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 3
ER -