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

doi:10.1194/jlr.M700409-JLR200

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 journal › Article › peer-review

22 Scopus citations

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	https://doi.org/10.1194/jlr.M700409-JLR200
State	Published - Mar 1 2008
Externally published	Yes

Keywords

Apolipoprotein E
Body mass index
Triglycerides
Very low density lipoprotein receptor

ASJC Scopus subject areas

Biochemistry
Endocrinology
Cell Biology

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Crawford, D. C., Nord, A., Badzioch, M. D., Ranchalis, J., McKinstry, L. A., Ahearn, M., Bertucci, C., Shephard, C., Wong, M., Rieder, M. J., Schellenberg, G. D., Nickerson, D. A., Heagerty, P. J., Wijsman, E. 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 journal › Article › peer-review

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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title = "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.",

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author = "Crawford, {Dana C.} and Alexander Nord and Badzioch, {Michael D.} and Jane Ranchalis and McKinstry, {Laura A.} and Magdalena Ahearn and Caterina Bertucci and Cynthia Shephard and Michelle Wong and Rieder, {Mark J.} and Schellenberg, {Gerard D.} and Nickerson, {Deborah A.} and Heagerty, {Patrick J.} and Wijsman, {Ellen M.} and Jarvik, {Gail P.}",

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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.

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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.

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