Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 8185134

Apolipoprotein E in hyperlipidemia.

C C Walden·R A Hegele
View original source ↗Export metadata ↓

Abstract

PURPOSE: To review DNA analysis of apolipoprotein E used to assess patients with hyperlipidemia. DATA SOURCES AND STUDY SELECTION: 44 basic science studies of molecular analysis; 42 basic science studies of the biochemical, cellular biological, and molecular biological features of apolipoprotein E; and 29 clinical investigational studies, meta-analyses, and case series of patients with mutations in apolipoprotein E. DATA EXTRACTION: Methods of DNA analysis were reviewed, using specific examples in human disease, and the role of apolipoprotein E in normal and disordered lipoprotein metabolism was reviewed. Genetic analysis of apolipoprotein E in populations and particularly in persons with type III hyperlipoproteinemia is reviewed. DATA SYNTHESIS: In the general population, common DNA variants of apolipoprotein E are consistently associated with modest differences in plasma lipids and lipoproteins. Homozygosity for the E2 isoform of apolipoprotein E predisposes some patients to the development of type III hyperlipoproteinemia, a condition that involves an additional genetic or environmental factor for full clinical expression. Rare mutations of apolipoprotein E also cause hyperlipidemia. CONCLUSIONS: DNA variation of apolipoprotein E is one of several genetic and environmental factors that interact in a complex manner to affect plasma lipoproteins. DNA analysis of apolipoprotein E can be used in persons with hyperlipidemia to identify those with type III hyperlipoproteinemia and in relatives of affected persons to identify those who are predisposed.

Explore related subjects

Apolipoproteins EBase SequenceGenetic TechniquesGenotypeHumansHyperlipoproteinemia Type IIIMolecular Sequence DataJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

C C Walden, R A Hegele. 1994-06-15. Apolipoprotein E in hyperlipidemia.. https://doi.org/10.7326/0003-4819-120-12-199406150-00009

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Informative-transmission disequilibrium test (i-TDT): combined linkage and association mapping that includes unaffected offspring as well as affected offspring.

To date, there is no test valid for the composite null hypothesis of no linkage or no association that utilizes transmission information from heterozygous parents to their unaffected offspring as well as the affected offspring from ascertained nuclear families. Since the unaffected siblings also provide information about linkage and association, we introduce a new strategy called the informative-transmission disequilibrium test (i-TDT), which uses transmission information from heterozygous parents to all of the affected and unaffected offspring in ascertained nuclear families and provides a valid chi-square test for both linkage and association. The i-TDT can be used in various study designs and can accommodate all types of independent nuclear families with at least one affected offspring. We show that the transmission/disequilibrium test (TDT) (Spielman et al. [1993] Am. J. Hum. Genet. 52:506-516) is a special case of the i-TDT, if the study sample contains only case-parent trios. If the sample contains only affected and unaffected offspring without parental genotypes, the i-TDT is equivalent to the sibship disequilibrium test (SDT) (Horvath and Laird [1998] Am. J. Hum. Genet. 63:1886-1897. In addition, the test statistic of i-TDT is simple, explicit and can be implemented easily without intensive computing. Through computer simulations, we demonstrate that power of the i-TDT can be higher in many circumstances compared to a method that uses affected offspring only. Applying the i-TDT to the Framingham Heart Study data, we found that the apolipoprotein E (APOE) gene is significantly linked and associated with cross-sectional measures and longitudinal changes in total cholesterol.

Apolipoproteins E↗
PubMed2007

Apolipoprotein E genotype affects the response to lipid-lowering therapy in Chinese patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the effect of apolipoprotein E (apoE) genotype on baseline lipid levels and the response to hydroxy-methyl glutaryl coenzyme A reductase inhibitors (statins) therapy in Chinese patients with type 2 diabetes mellitus (DM). RESEARCH DESIGN AND METHODS: We consecutively recruited Chinese patients with type 2 DM requiring lipid-lowering therapy according to current guidelines. Patients were started on either simvastatin 10 mg daily or given an equivalent dose of lovastatin 20 mg. After 12 weeks of statin therapy, patients had fasting lipid profiles repeated. ApoE genotyping was performed by restriction fragment length polymorphism (RFLP). RESULTS: Ninety-six patients were studied. The epsilon3/epsilon3 genotype was in 62.5%, epsilon2/epsilon3 and epsilon3/epsilon4, 16.7 and 20.8%, respectively. After adjusting for confounding variables, baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in those with epsilon3/epsilon4 compared with epsilon2/epsilon3 genotype (6.7 vs. 5.5 mm for TC, 4.5 vs. 3.6 mm for LDL-C; p = 0.015 and p = 0.025, respectively). With statin therapy, epsilon3/epsilon4 patients had significantly greater LDL-C lowering compared with epsilon2/epsilon3 patients (48 vs. 27.7%; p = 0.04). There was no gender difference in baseline lipid parameters or response to statin therapy. CONCLUSIONS: ApoE genotype accounts for interindividual variability of baseline cholesterol levels, and response to statin therapy in Chinese patients with type 2 DM.

Apolipoproteins E↗
PubMed2007

Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family members.

We examined the role of hepatic heparan sulfate in triglyceride-rich lipoprotein metabolism by inactivating the biosynthetic gene GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) in hepatocytes using the Cre-loxP system, which resulted in an approximately 50% reduction in sulfation of liver heparan sulfate. Mice were viable and healthy, but they accumulated triglyceride-rich lipoprotein particles containing apoB-100, apoB-48, apoE, and apoCI-IV. Compounding the mutation with LDL receptor deficiency caused enhanced accumulation of both cholesterol- and triglyceride-rich particles compared with mice lacking only LDL receptors, suggesting that heparan sulfate participates in the clearance of cholesterol-rich lipoproteins as well. Mutant mice synthesized VLDL normally but showed reduced plasma clearance of human VLDL and a corresponding reduction in hepatic VLDL uptake. Retinyl ester excursion studies revealed that clearance of intestinally derived lipoproteins also depended on hepatocyte heparan sulfate. These findings show that under normal physiological conditions, hepatic heparan sulfate proteoglycans play a crucial role in the clearance of both intestinally derived and hepatic lipoprotein particles.

Apolipoproteins E↗