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

Dana C. Crawford, Alexander 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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)588-596
Number of pages9
JournalJournal of Lipid Research
Volume49
Issue number3
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Fingerprint

Carotid Artery Diseases
Polymorphism
Genotype
Single Nucleotide Polymorphism
Body Mass Index
Ligands
5' Flanking Region
Apolipoproteins B
Lipid Metabolism
Pathologic Constriction
Nucleotides
Genes
VLDL receptor
Lipids
Population

Keywords

  • Apolipoprotein E
  • Body mass index
  • Triglycerides
  • Very low density lipoprotein receptor

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Crawford, D. C., Nord, A., Badzioch, M. D., Ranchalis, J., McKinstry, L. A., Ahearn, M., ... Jarvik, G. P. (2008). A common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk. Journal of Lipid Research, 49(3), 588-596. https://doi.org/10.1194/jlr.M700409-JLR200

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 journalArticle

Crawford, DC, Nord, A, Badzioch, MD, Ranchalis, J, McKinstry, LA, Ahearn, M, Bertucci, C, Shephard, C, Wong, M, Rieder, MJ, Schellenberg, GD, Nickerson, DA, Heagerty, PJ, Wijsman, EM & Jarvik, GP 2008, 'A common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk', Journal of Lipid Research, vol. 49, no. 3, pp. 588-596. https://doi.org/10.1194/jlr.M700409-JLR200
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. / A common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk. In: Journal of Lipid Research. 2008 ; Vol. 49, No. 3. pp. 588-596.
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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.",
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