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; 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.

doi:10.1194/jlr.m700409-jlr200

Cited by 24 publications

(21 citation statements)

References 71 publications

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“…Collectively, these kinetic defects may account for the dyslipoproteinemia seen in our apoE2/E2 type III hyperlipidemic subjects. Whether downregulation of VLDL receptors or other extrahepatic receptors ( 31,32 ), or the inhibition of lipolytic enzymes by other apoproteins, such as apoC-III ( 33,34 ), contributes further to the impaired catabolism and accumulation of ␤ -VLDL particles in circulation requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Effect of apolipoprotein E genotype on apolipoprotein B-100 metabolism in normolipidemic and hyperlipidemic subjects

Ooi

Janus

Grant

et al. 2010

Journal of Lipid Research

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Apolipoprotein (apo) E is a 34.2 kDa glycoprotein synthesized by the liver and to a lesser extent by peripheral tissues ( 1 ). It is associated in plasma with triglyceride-rich lipoproteins (TRL) and HDL particles ( 2 ). ApoE plays a central role in mediating hepatic recognition and uptake of TRL and their remnants by acting as a ligand for lipoprotein binding to the LDL receptor, LDL receptorrelated protein, and glycosaminoglycans ( 3 ). ApoE may also activate enzymes involved in lipoprotein metabolism, including hepatic lipases, cholesteryl ester transfer protein, and lecithin cholesteryl:acytransferase ( 4 ). The apoE gene is polymorphic, with three common alleles coding for three major isoforms identifi ed as E2, E3, and E4 ( 5 ).Type III hyperlipidemia, also known as dysbetalipoproteinemia, is a rare form of genetic dyslipidemia characterized by elevated plasma cholesterol and triglycerides and the presence of cholesterol-enriched remnant particles, collectively known as ␤ -VLDL ( 6 ). The accumulation of ␤ -VLDL particles may be associated with impaired TRL catabolism ( 7 ). Type III hyperlipidemic subjects may have severe xanthomatosis and signifi cantly increased risk of developing premature atherosclerosis ( 8 ). The majority of type III hyperlipidemic subjects are homozygotes for the apoE2 allele of the apoE ( APOE ) gene. However, <10% of apoE2 homozygotes develop hyperlipidemia, and most apoE2/E2 subjects are either normolipidemic or hypocholesterolemic ( 6 ). The onset of hyperlipidemia may be associated with additional genetic factors and/or environmental factors such as obesity, diabetes, and menopausal status ( 6 ). The regulation of lipoprotein transport in subjects with the apoE2/E2 genotype, in particular those withAbstract The effect of apolipoprotein (apo) E genotype on apoB-100 metabolism was examined in three normolipidemic apoE2/E2, fi ve type III hyperlipidemic apoE2/E2, and fi ve hyperlipidemic apoE3/E2 subjects using simultaneous administration of 131 I-VLDL and 125 I-LDL, and multicompartmental modeling. Compared with normolipidemic apoE2/E2 subjects, type III hyperlipidemic E2/E2 subjects had increased plasma and VLDL cholesterol, plasma and VLDL triglycerides, and VLDL and intermediate density lipoprotein (IDL) apoB concentrations ( P < 0.05). These abnormalities were chiefl y a consequence of decreased VLDL and IDL apoB fractional catabolic rate (FCR). Compared with hyperlipidemic E3/E2 subjects, type III hyperlipidemic E2/E2 subjects had increased IDL apoB concentration and decreased conversion of IDL to LDL particles ( P < 0.05). In a pooled analysis, VLDL cholesterol was positively associated with VLDL and IDL apoB concentrations and the proportion of VLDL apoB in the slowly turning over VLDL pool, and was negatively associated with VLDL apoB FCR after adjusting for subject group. VLDL triglyceride was positively associated with VLDL apoB concentration and VLDL and IDL apoB production rates after adjusting for subject group. A defective apoE contributes to altered lipoprotein me...

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Section: Discussionmentioning

confidence: 99%

Effect of apolipoprotein E genotype on apolipoprotein B-100 metabolism in normolipidemic and hyperlipidemic subjects

Ooi

Janus

Grant

et al. 2010

Journal of Lipid Research

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“…This study has been previously described in detail elsewhere ( 27 ). Briefl y, the study gains power per sampled individual from using a tails-of-the-distribution sampling scheme where cases (n = 442) had >80% stenosis of one or both internal carotid arteries, and controls (n = 497) had <15% stenosis bilaterally on duplex ultrasound.…”

Section: Samplementioning

confidence: 99%

Genetic and nongenetic sources of variation in phospholipid transfer protein activity

Jarvik

Rajagopalan

Rosenthal

et al. 2010

Journal of Lipid Research

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“…In addition, since the absence of VLDLR leads to non-obesity in mice, it is assumed that this gene is associated with obesity (Goudriaan et al, 2001). The same principle applies to humans: those with VLDLR gene mutations have lower body weight compared with the control group (Boycott et al, 2005;Crawford et al, 2008). Therefore, VLDLR were confirmed to be associated with body weight and obesity in humans and mice (Brockmann et al, 1998;Kunej et al, 2012;Clemente-Postigo et al, 2011).…”

Section: Introductionmentioning

confidence: 91%

A Novel Polymorphism of VLDLR Signal Peptide Coding Region and Its Association with Growth and Abdominal Fat Traits of Gaoyou Domestic Ducks

Mingliang

Cong

Xuan

et al. 2017

Rev. Bras. Cienc. Avic.

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The VLDLR gene plays important roles in the growth and adiposity in humans and mice. The purpose of this study was to investigate the relationship between VLDLR gene genetic polymorphisms and growth and abdominal fat traits of the Gaoyou domestic duck. A total of 267 Gaoyou ducks were employed for testing. A 18bp deletion was identified in VLDLR signal peptide coding region. The results of χ 2 test suggested that the genotype frequencies of VLDLR signal peptide coding region were not in Hardy-Weinberg equilibrium. Least squares analysis showed that body weight (BW) of -18bp/-18bp genotype ducks was significantly higher than those of other genotypes from six (BW6) (p<0.05) to ten weeks of age (BW10) (p<0.01). The association analysis was performed taken body weight as covariant for abdominal percentage (AFP). Results showed that there was not interaction between genotype (p>0.05) and body weight for AFP and different genotypes had a significant effect on AFP (p<0.05). The results of Bonferroni t-test revealed that the abdominal fat percentage (AFP) of -18bp/-18bp genotype was significantly lower than those of +18bp/-18bp (p<0.05). Preliminary studies have shown that VLDLR may be a candidate gene for the selection for growth and abdominal fat, and the results of the present study indicate that VLDLR strongly influences carcass abdominal fat content of Gaoyou ducks.

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

Cited by 24 publications

References 71 publications

Effect of apolipoprotein E genotype on apolipoprotein B-100 metabolism in normolipidemic and hyperlipidemic subjects

Effect of apolipoprotein E genotype on apolipoprotein B-100 metabolism in normolipidemic and hyperlipidemic subjects

Genetic and nongenetic sources of variation in phospholipid transfer protein activity

A Novel Polymorphism of VLDLR Signal Peptide Coding Region and Its Association with Growth and Abdominal Fat Traits of Gaoyou Domestic Ducks

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