Interpretive Handbook

Test 80905 :
Apolipoprotein E Genotyping, Blood

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Apolipoproteins are structural constituents of lipoprotein particles that participate in lipoprotein synthesis, secretion, processing, and metabolism. Apolipoproteins have critical roles in blood lipid metabolism. Defects in apolipoprotein E (Apo E) are responsible for familial dysbetalipoproteinemia, or type III hyperlipoproteinemia, in which increased plasma cholesterol and triglycerides result from impaired clearance of chylomicron and very-low-density lipoprotein (VLDL) remnants.


The human APOE gene is located on chromosome 19. The 3 common APOE alleles are designated e2, e3, and e4, which encode the Apo E isoforms E2, E3, and E4, respectively. E3, the most common isoform in Caucasians, shows cysteine (Cys) at amino acid position 112 and arginine (Arg) at position 158. E2 and E4 differ from E3 by single amino acid substitutions at positions 158 and 112, respectively (E2: Arg158->Cys; E4: Cys112->Arg). The allele frequencies for most Caucasian populations are as follows:

-e2=8% to 12%

-e3=74% to 78%

-e4=14% to 15%


E2 and E4 are both associated with higher plasma triglyceride concentrations. Over 90% of individuals with type III hyperlipoproteinemia are homozygous for the e2 allele. However, <10% of individuals homozygous for the e2 allele have overt type III hyperlipoproteinemia. This suggests that other genetic, hormonal, or environmental factors must contribute to the phenotypic expression of the disease. The e4 allele has been linked to pure elevations of low-density lipoproteins (LDL). Patients with a lipid profile consistent with type III hyperlipidemia are candidates for analysis of their APOE genotype.

Useful For Suggests clinical disorders or settings where the test may be helpful

Determining the specific apolipoprotein E genotypes in patients with type III hyperlipoproteinemia

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This assay will not detect all of the mutations that cause type III hyperlipoproteinemia. Therefore, the absence of a detectable mutation(s) does not rule out the possibility that an individual is a carrier of or affected with this disease.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


In rare cases, DNA alterations of undetermined significance may be identified.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.


This test is not available for Alzheimer's disease testing or when the reason for referral indicates "dementia."


This assay does not identify all of the less common apolipoprotein E alleles. Thus, an individual who appears to be homozygous for e2, e3, or e4 may carry 1 of the rare alleles that cannot be detected by this assay.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

The apolipoprotein E gene alleles will be reported.

Expected values: e2e2, e2e3, e2e4, e3e3, e3e4, e4e4

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Smelt AH, de Beer F: Apolipoprotein E and familial dysbetalipoproteinemia: Clinical, biochemical, and genetic aspects. Semin Vasc Med 2004;4(3):249-257

2. Utermann G: Morgagni lecture: genetic polymorphism of apolipoprotein E-impact on plasma lipoprotein metabolism In Diabetes, Obesity and Hyperlipidemias. Edited by G Crepaldi, A Tiengo, G Baggio. Amsterdam. Elsevier, 1985, pp 1–28

3. Elosua R, Ordovas JM, Cupples LA, et al: Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study. J Lipid Res 2004;45(10):1868-1875