Apolipoprotein E Genotyping (ApoE)

Background:
Apolipoprotein E is involved in the secretion, synthesis, and, metabolism of lipoproteins in the circulation.  The gene for apolipoprotein E (APOE) maps to chromosome 19q13.2.  This gene is highly polymorphic.  The three common alleles, e2, e3, and e4, differ only by a single amino acid substitution as indicated below.  Average allele frequencies in various populations are indicated in parentheses; however, these values may differ between ethnic populations. 

e2: cys112, cys158 (11%)

e3: cys112, arg158 (72%)

e4: arg112, arg158 (17%)

These apoE variants differ in function by their ligand-binding affinity for apoE receptors and are involved in the maintenance of cholesterol and triglycerides in the blood.

Reasons for Referral:

APOE genotyping may provide additional information toward the risk or diagnosis of:

• Familial hyperlipoproteinemia type III (dysbetalipoproteinemia)
• Coronary artery disease
• Cholesterol

• High blood pressure

· Alzheimer disease. 

Method:
Direct DNA analysis: PCR-based assay with restriction enzyme digestion (HhaI) will identify the three most common APOE alleles, e2, e3, and e4.  Less common variants will not be detected.

Interpretation and Reporting:

The patient's genotype will be reported. 

The following clinical associations with APOE genotypes have been reported but are not diagnostic:

• e2,e2:  hyperlipoproteinemia type III (dysbetalipoproteinemia)  1-5% develop disease
• e4,e4;  increased risk for coronary artery disease (elevated plasma cholesterol, LDL, ApoB, LpA)
• e3,e4: Increased risk of elevated systolic blood pressure and early myocardial infarction

A single e2 or e4 allele can predispose a patient to elevated plasma cholesterol and triglyceridemia.

Analytic Time:  14 days.