Test Id : APOEG

Specimen preferred to arrive within 96 hours of collection.

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

Container/Tube:

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.

• Informed Consent for Genetic Testing
• Molecular Genetics: Neurology Patient Information
• Informed Consent for Genetic Testing (Spanish)

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.

1 mL

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

Determining the specific apolipoprotein E (APOE) genotypes that may increase risk for amyloid related imaging abnormalities in individuals being treated for Alzheimer disease with B-amyloid-targeting antibodies

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.

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.

Additionally, according to the US Food and Drug Administration label, the APOE e4 allele in the context of amyloid-targeting antibody treatments for Alzheimer disease has been associated with a higher incidence of amyloid related imaging abnormalities.

An interpretive report will be provided.

This assay will not detect all of the genetic variants that cause type III hyperlipoproteinemia. Therefore, the absence of a detectable genetic variant 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 the interpretation of results may occur if information given is inaccurate or incomplete.

Rare variants (ie, 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 one of the rare alleles that cannot be detected by this assay.

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: Crepaldi G, Tiengo A, Baggio G (eds). Diabetes, Obesity and Hyperlipidemias 3: Proceedings of the 4th European Symposium on Metabolism. 1985. Elsevier; 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(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;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;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 www.choosingwisely.org/societies/american-college-of-medical-genetics-and-genomics/

8. Filippi M, Cecchetti G, Spinelli EG, Vezzulli P, Falini A, Agosta F. Amyloid-Related Imaging Abnormalities and B-Amyloid-Targeting Antibodies: A Systematic Review. JAMA Neurol. 2022;79(3):291-304

A polymerase chain reaction-based assay, which includes HhaI digestion of the amplified product, is utilized to identify the 3 most common apolipoprotein E alleles (e2, e3, e4).(Unpublished Mayo method)

Tuesday, Thursday

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

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