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

被引：25

作者：

Crawford, Dana C. ^{[2
]}

Nord, Alex S. ^{[1
]}

Badzioch, Michael D. ^{[1
]}

Ranchalis, Jane ^{[1
]}

McKinstry, Laura A. ^{[1
]}

Ahearn, Magdalena ^{[3
]}

Bertucci, Caterina ^{[3
]}

Shephard, Cynthia ^{[3
]}

Wong, Michelle ^{[3
]}

Rieder, Mark J. ^{[3
]}

Schellenberg, Gerard D. ^{[1
,5
,6
]}

Nickerson, Deborah A. ^{[3
]}

Heagerty, Patrick J. ^{[4
]}

Wijsman, Ellen M. ^{[1
,4
]}

Jarvik, Gail P. ^{[1
]}

机构：

[1] Univ Washington, Dept Med, Seattle, WA 98195 USA

[2] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet Res, Nashville, TN 37232 USA

[3] Univ Washington, Div Med Genet, Dept Genome Sci, Seattle, WA 98195 USA

[4] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[5] Univ Washington, Dept Neurol, Seattle, WA 98195 USA

[6] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA

来源：

JOURNAL OF LIPID RESEARCH | 2008年 / 49卷 / 03期

关键词：

very low density lipoprotein receptor; apolipoprotein E; body mass index; triglycerides;

D O I：

10.1194/jlr.M700409-JLR200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.jr These findings may further our understanding of VLDLR function, its ligand APOE, and ultimately the pathogenesis of CAAD in the general population.

引用

页码：588 / 596

页数：9

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