Apolipoprotein E phenotypes in hyperlipidaemic patients and their implications for treatment

Janus, Edward; Grant, Susan; Lintott, Caroline J.; Wardell, Mark R.

doi:10.1016/0021-9150(85)90038-3

Cited by 15 publications

(8 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The seven type III patients in this study were part of a group of 32 type III subjects with the apo E-2/2 phenotype, whose plasma and lipoprotein lipid values have already been reported (44). All were undergoing dietary and clofibrate treatment that had successfully lowered their plasma cholesterol and triglyceride levels to normal values (Table I).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.

Wardell¹,

Brennan²,

Janus³

et al. 1987

J. Clin. Invest.

139

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

“…Affected subjects are often homozygous for apo E2, but heterozygosity for this variant has also been reported in association with this disease (4)(5)(6)(7)(8). Individual cases of type III have also been observed in association with the apo E-3/3 phenotype (9) and in an individual with a deficiency of apo E (10).…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.

Wardell¹,

Brennan²,

Janus³

et al. 1987

J. Clin. Invest.

139

View full text Add to dashboard Cite

show abstract

“…83 This enrichment in the frequency of the e2 allele was associated with hypertriglyceridemia 65 84 A higher prevalence of the e4 allele 81 ' M or of the E4/4 phenotype w was associated with hypercholesterolemia in some studies. When subjects with hypertriglyceridemia and a type IV hyperiipoproteinemia phenotype were evaluated in more detail, a higher prevalence of the e2 allele was found only in the group of subjects with normal apo B levels, and subjects with combined hypertriglyceridemia and hyperapobetalipoproteinemia had a normal apo E isoform distribution.…”

Section: Association Of Apo E Phenotypes With Other Forms Of Hyperiipmentioning

confidence: 95%

Apolipoprotein E polymorphism and atherosclerosis.

1988

View full text Add to dashboard Cite

Lipoproteins play a central role in the development of atherosclerotic cardiovascular disease in humans. The plasma concentrations of lipoproteins and their metabolic fates are modulated by apolipoproteins on the surface of these lipid-rich particles. The hypothesis has been raised that genetic variation in apolipoproteins is a major determinant of the interindividual variation in susceptibility to coronary artery disease (CAD). In humans, the structural gene locus for plasma apolipoprotein E (apo E) is polymorphic:1 " 6 three common alleles, designated e4, e3, and e2, code for three major apo E isoforms in plasma, respectively designated apo E4, apo E3, and apo E2. Apo E is a key protein in the modulation of the metabolism of the highly atherogenic apo B-containing lipoproteins. Therefore, apo E provides a good model to test the above hypothesis.The existence of a polymorphism for such an important apolipoprotein has been a source of major interest in recent years and has raised many questions for clinicians, epidemiologists, geneticists, and biochemists. The similarities of the relative frequencies of the three common alleles among populations representing very different ethnic, cultural, and geographic settings; their different effects on •lipoprotein metabolism; and their association with certain lipid transport disorders have stimulated research aimed at a better understanding of their role in health and disease. A wealth of information 7 " 18 has accrued from studies on apolipoprotein E structure, metabolism, and function. These have considerably advanced our knowledge of the role of apo E in normal and abnormal lipoprotein metabolism, the complex interactions leading to hyperfipidemia and atherosclerosis, and the pathogenesis of type III hyperiipoproteinemia. Of major interest is the observation that the protein products of the e4 and E2 alleles have separate, and in some circumstances opposite, influences on plasma lipo- protein concentrations, a finding which leads to the hypothesis that the apo E polymorphism ranks among the major factors involved in determining interindividual differences in the initiation and progression of atherosclerosis. The evidence associating the apo E polymorphism with altered lipid and lipoprotein levels and atherosclerosis will be reviewed here. First, the apo E gene and gene product will be considered with a brief overview of molecular biology, protein chemistry, and methods for phenotyping. Second, the impact of variation at the apo E locus on plasma lipids and lipoproteins in health and disease will be discussed. Third, the metabolic interactions accounting for the various effects of the different alleles on lipids and lipoproteins will be considered to provide a unifying interpretation as to how apo E modulates the metabolism of apo B-containing lipoproteins and their remnants. Last, direct evidence associating the apo E polymorphism and atherosclerosis will be reviewed and discussed. This review is not intended to be all-inclusive, and the reader is referred to recent r...

show abstract

“…Lipoprotein electrophoresis was performed according to the Helena Laboratories method on cellulose acetate strips (Chemac Laboratories Ltd., New Zealand) (9)(10)(11)17 ).…”

Section: Additional Analysesmentioning

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

Self Cite

View full text Add to dashboard Cite

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...

show abstract

Apolipoprotein E phenotypes in hyperlipidaemic patients and their implications for treatment

Cited by 15 publications

References 21 publications

Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.

Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.

Apolipoprotein E polymorphism and atherosclerosis.

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

Contact Info

Product

Resources

About