Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review

Area of Science:

• Genetics
• Cardiovascular Science
• Metabolic Disorders

Background:

• The apolipoprotein E (apoE) gene, located on chromosome 19q13.2, exhibits common polymorphisms with alleles (*)\\epsilon2, (*)\\epsilon3, and (*)\\epsilon4.
• Apo(*) Epsilon3 is the most prevalent allele (>60%) across diverse populations.
• Apolipoprotein E plays a crucial role in lipoprotein metabolism and cholesterol regulation.

Purpose of the Study:

• To review the association between apolipoprotein E gene polymorphism, cholesterol metabolism, and cardiovascular disease.
• To explore the functional impact of apoE variants on lipoprotein binding, uptake, and catabolism.
• To examine the relationship between apoE genotypes and various lipid disorders and vascular conditions.

Main Methods:

• Literature review of studies investigating apolipoprotein E gene polymorphism.
• Analysis of functional effects on hepatic lipoprotein processing via LDL receptor and apoE-specific receptors.
• Correlation of apoE allelic variation with plasma lipid concentrations (total cholesterol, LDL cholesterol, apo B).

Main Results:

• Apolipoprotein E polymorphism significantly influences plasma lipid concentrations and is associated with hyperlipoproteinemia type III, coronary heart disease, stroke, peripheral artery disease, and diabetes mellitus.
• Despite modest associations with plaque and coronary heart disease, apoE genotype has poor predictive value for clinically defined atherosclerosis.
• ApoE alleles and isoforms are also linked to neurodegenerative conditions, notably Alzheimer's disease.

Conclusions:

• Apolipoprotein E gene polymorphism is a key factor in cholesterol metabolism and cardiovascular disease risk.
• The predictive utility of apoE genotyping for atherosclerosis screening is limited.
• Further research into apoE's role in both vascular and neurological disorders is warranted.