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Test ID: APOEG Apolipoprotein E Genotyping, Blood

Useful For

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.

Method Name

Polymerase Chain Reaction (PCR) including Restriction Digest

Reporting Name

Apolipoprotein E Genotyping, B

Specimen Type


Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Specimen Type: Whole blood


Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert whole blood several times to mix blood. Do not aliquot.

2. Send specimen in original tube.

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)

Clinical Information

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 (ApoE) 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 remnants.


The human APOE gene is located on chromosome 19. The 3 common APOE alleles are designated e2, e3, and e4, which encode the ApoE isoforms E2, E3, and E4, respectively. E3, the most common isoform in the White population, 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 White 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, less than 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. 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 and Genomics due to limited clinical utility and poor predictive value.


An interpretive report will be provided.

Clinical Reference

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

2. Utermann G: Morgagni lecture: genetic polymorphism of apolipoprotein E-impact on plasma lipoprotein metabolism In: Crepaldi G, Tiengo A, Baggio G. Diabetes, Obesity and Hyperlipidemias 3: Proceedings of the 4th European Symposium on Metabolism 1985. Elsevier; 1985:1-28

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 Oct;45(10):1868-1875

4. Poirier J, Davignon J, Bouthillier D, et al: Apolipoprotein E polymorphism and Alzheimer's disease. Lancet. 1993 Sep;342(8873): 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 Oct 22-29;278(16):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 Jun;13(6):597-605

7. American College of Medical Genetics and Genomics: Five things physicians and patients should question. Choosing Wisely; 2015. Updated July 1, 2021. Accessed October 27, 2021. Available at

Day(s) Performed


Report Available

9 to 10 days

CPT Code Information

81401-APOE (apolipoprotein E) (eg, hyperlipoproteinemia type III, cardiovascular disease, Alzheimer disease), common variants (eg, *2, *3, *4)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
APOEG Apolipoprotein E Genotyping, B 42315-2


Result ID Test Result Name Result LOINC Value
53198 Result Summary 50397-9
53199 Result 42315-2
53200 Interpretation 69047-9
53201 Reason for Referral 42349-1
53202 Specimen 31208-2
53203 Source 31208-2
53204 Released By 18771-6

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.


1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file.

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Neurology Patient Information

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Specimen Minimum Volume

1 mL

Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information: