Test Catalog

Test ID: APOEG    
Apolipoprotein E Genotyping, Blood

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

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


APOE genotyping has been used to assess susceptibility for Alzheimer disease. However, the use of APOE analysis for predictive testing for Alzheimer disease is not currently recommended by the American College of Medical Genetics due to limited clinical utility and poor predictive value.

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.


The APOE gene is also a known susceptibility gene for Alzheimer disease. The e4 allele is associated with an increased risk for Alzheimer disease, particularly late-onset disease, in a dose-dependent manner. This risk is also influenced by other factors. It is estimated that individuals with the APOE e3/e4 genotype have a 4-fold relative risk for Alzheimer disease, while homozygotes for e4 allele have a 12-fold relative risk. Several studies have suggested a protective effect of the APOE e2 allele.


The APOE e4 allele, however, is neither sufficient nor necessary for the development of Alzheimer disease.


Approximately 50% of individuals with Alzheimer disease carry an e4 allele and many individuals who have an e4 allele will never develop Alzheimer disease. The use of APOE analysis for predictive testing for Alzheimer disease is not currently recommended by the American College of Medical Genetics due to limited clinical utility and poor predictive value.

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 does not rule out the possibility that an individual is a carrier of or affected with this disease.


This assay cannot predict or rule out the development of Alzheimer disease in an individual.


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.


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.

Clinical Reference Recommendations for 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

4. Poirier J, Davignon J, Bouthillier D, et al: Apolipoprotein E polymorphism and Alzheimer’s disease. Lancet 1993;342: 697-699

5. Farrer L, Cupples A, Haines J, et al: Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. JAMA 1997;278:1349-1356

6. Goldman JS, Hahn SE, Catania JW, et al: Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med 2011;13(6):597-605

7. American College of Medical Genetics and Genomics 2015 July 10. Available at: www.choosingwisely.org/societies/american-college-of-medical-genetics-and-genomics/

Special Instructions Library of PDFs including pertinent information and forms related to the test