Were you looking instead for APOE genotyping ordered to evaluate for Alzheimer disease? If so, see APOE Genotyping, Alzheimer Disease.
At a Glance
Why Get Tested?
APOE genotype tests are most often done as part of research protocols to help understand the role of genetic factors in cardiovascular disease. However, the testing is sometimes used in clinical settings to help confirm a diagnosis of type III hyperlipoproteinemia (also known as familial dysbetalipoproteinemia).
When to Get Tested?
A blood sample drawn from a vein in your arm
Test Preparation Needed?
The Test Sample
What is being tested?
Apolipoprotein E (Apo E) is a protein that helps transport lipids (fats and cholesterol) in the blood. It is recognized by specific cell surface receptors that allow it to deliver lipids to cells for use or storage and to deliver excess lipid to the liver for excretion.
The ApoE protein has three genetic forms that have slightly different compositions. They are called ApoE2, ApoE3, and ApoE 4. ApoE2 is poorly recognized by cell surface receptors whereas ApoE3 and ApoE4 bind tightly to those receptors. Therefore, people with ApoE2 tend to have higher blood lipids since delivery from blood to cells is impaired by poor binding of ApoE2 to receptors.
Three different genes (termed alleles) are designated as e2, e3, and e4 and code respectively for ApoE2, ApoE3, and ApoE4. Each person inherits one allele from each parent. A person who has the same allele from each parent is termed homozygous: e2/e2 or e3/e3 or e4/e4. One who has different alleles is termed heterozygous: e2/e3 or e2/e4 or e3/e4.
APOE e3/e3 is the most common genotype (seen in about 63% of the population) and is considered "neutral." Risks of disease are made relative to the e3/e3 population.
APOE e4 (as e4/e4 and e4/e3) is found in 25% of the population and is associated with an increased risk of atherosclerosis. People with these genotypes could be predisposed to a significantly elevated level of LDL-C ("bad cholesterol") and triglycerides when their diet is high in saturated fat.
People with the APOE e2 allele tend to have lower LDL-C levels but elevated triglycerides. APOE e2 is also associated with type III hyperlipoproteinemia/hyperlipidemia (HPL III or familial dysbetalipoproteinemia), a rare inherited disorder that causes fatty yellowish deposits on the skin called xanthomas, increased triglycerides in the blood, and atherosclerosis that develops at an early age. However, only about 2% of people with the e2/e2 genotype develop type III hyperlipoproteinemia/hyperlipidemia.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
Ask a Laboratory Scientist
NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Sources Used in Current Review
(August 10, 2009) Ward H, et. al. APOE Genotype, Lipids, and Coronary Heart Disease Risk, A Prospective Population. Arch Intern Med. 2009;169(15):1424-1429. Available online at http://archinte.jamanetwork.com/article.aspx?articleid=1108512 through http://archinte.jamanetwork.com. Accessed October 2013.
(2013) Yan-Wei Yin, et al. Association between Apolipoprotein E Gene Polymorphism and the Risk of Coronary Artery Disease in Chinese Population: Evidence from a Meta-Analysis of 40 Studies. PLoS ONE 8(6): e66924. doi:10.1371/journal.pone.0066924. Available online at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0066924 through http://www.plosone.org. Accessed October 2013.
Henry's Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2011, 230-231.
(December 2, 2010) Citkowitz E. Dysbetalipoproteinemia Workup. Medscape Reference. Available online at http://emedicine.medscape.com/article/118466-workup through http://emedicine.medscape.com. Accessed October 2013.
(2007) Bennet A, et al. Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 2007; 298(11):1300. Abstract available online at http://www.ncbi.nlm.nih.gov/pubmed/17878422 through http://www.ncbi.nlm.nih.gov. Accessed October 2013.
(2008) Donnelly L, et al. Apolipoprotein E genotypes are associated with lipid lowering responses to statin treatment in diabetes: a Go-DARTS study. Pharmacogenet Genomics 2008; 18(4):279. Abstract available online at http://www.ncbi.nlm.nih.gov/pubmed/18334912 through http://www.ncbi.nlm.nih.gov. Accessed October 2013.
(2012) Ciftdogan D et al. The association of apolipoprotein E polymorphism and lipid levels in children with a family history of premature coronary artery disease. J Clin Lipidol 2012; 6(1):81. Abstract available online at http://www.ncbi.nlm.nih.gov/pubmed/22264578 through http://www.ncbi.nlm.nih.gov. Accessed October 2013.
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER, Bruns DE, eds. 4th edition, St. Louis: Elsevier Saunders; 2006, Pp 930-931.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.
Sloane, P. (1998, November 1). Advances in the Treatment of Alzheimer's Disease. American Family Physician by the American Academy of Family Physicians [On-line journal]. Available online at http://www.aafp.org/afp/981101ap/sloane.html through http://www.aafp.org.
Eastman, P. (2002 March). Keeping Alzheimer's at Bay, Early Diagnosis Keeps Patients Functioning Longer. AARP Bulletin Online [On-line serial]. Available online at http://www.aarp.org/bulletin/departments/2002/health/0310_health_1.html through http://www.aarp.org.
McConnell, S., et. al. Unraveling the Mysteries of Alzheimer's Disease: Exciting New Developments in Research. From panel sponsored by the Alzheimer's Association [On-line information]. Available online at http://www.asaging.org/am/cia2/alzheimer.html through http://www.asaging.org.
Galasko, D., et. al. (1998). High Cerebrospinal Fluid Tau and Low Amyloid b42 Levels in the Clinical Diagnosis of Alzheimer Disease and Relation to Apolipoprotein E Genotype. Arch Neurol [On-line journal], vol (55) pages (937-945). Available online at http://archneur.ama-assn.org/issues/v55n7/abs/noc7433.html through http://archneur.ama-assn.org.
ARF (1996-2002). Standard Medical Workup for Alzheimer's Disease. Alzheimer Research Forum [On-line information]. Available online at http://www.alzforum.org/members/research/treatment_guide/workup.html through http://www.alzforum.org.
Family Caregiver Alliance. Fact Sheet: Alzheimer's Disease [On-line information]. Available online at http://www.caregiver.org/factsheets/diagnoses/alzheimersC.html through http://www.caregiver.org.
Bird, T. (2001 June 22 last update). Alzheimer Overview. GeneReviews [On-line information]. Available online through http://www.genetests.org.
Gottlieb, F. and Lambert, J. G. (2002, January 2, last update). Alzheimer’s Disease. MEDLINEplus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000760.htm.
Miller, M. (1998 February 18). 26 national Alzheimer's Disease Centers Collaborate on Study of the Utility of Genetic Testing for Alzheimer’s. National Institutes of Health News Release [On-line press release]. Available online at http://www.nia.nih.gov/news/pr/1998/02%2D18.htm through http://www.nia.nih.gov.
NIH (2000). Progress report on Alzheimer's disease, taking the next steps. NIH Publication No. 00-4859 [On-line report]. Available online at http://www.alzheimers.org/pubs/prog00.htm#Introduction through http://www.alzheimers.org.
UniSci (2002, April 08). New Approaches Seen For Early Alzheimer's Diagnosis. Daily University Science News [On-line Article]. Review of two studies found in Neuropsychology, Vol 16 (2). Available online at http://unisci.com/stories/20022/0408025.htm through http://unisci.com.
Eldercare (2002 February 28, last update). Is it Alzheimer's ... or Just Forgetfulness? Sponsored by Nebraska's Area Agencies on Aging [On-line information]. Available online at http://nncf.unl.edu/eldercare/info/lifeline/LLforget.html through http://nncf.unl.edu.
Hain, T. (2000 February 13). Alzheimer's Disease. Neurology, Northwestern University Medical School [3rd year neurology medical student curriculum material]. Available online at http://www.neuro.nwu.edu/meded/behavioral/alzheimers.html through http://www.neuro.nwu.edu.
Kleiner-Fisman, G., Updated by (2002 January 2, last update). CSF Collection. MEDLINEplus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003428.htm.
MEDLINEplus, (2001 November 20). Familial dysbetalipoproteinemia. MEDLINEplus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000402.htm.
Eichner, J., et. al. (2002, March 15). Apolipoprotein E Polymorphism and Cardiovascular Disease. HuGE Review, appeared in Am J Epidemiol 2002 [On-line journal], 155(6): 487-95. Available online at http://www.cdc.gov/genomics/hugenet/reviews/APOEcardio.htm through http://www.cdc.gov.
MEDLINEplus, (2001 October 29). Familial hypercholesterolemia. MEDLINEplus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000392.htm.
Stephen P. Day, Ph.D. Director, Medical Affairs, Third Wave Molecular Diagnostics.
Robert C. Green, M.D., M.P.H. Professor of Neurology, Genetics and Epidemiology. Director, Alzheimer's Disease Clinical and Research Program. Boston University Schools of Medicine and Public Health, Boston, MA.
Ian R.A. Mackenzie, MD FRCPC. Department of Pathology, Vancouver General Hospital, British Columbia, Canada.
Pagana, K. D. & Pagana, T. J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 110-114.
(Updated 2009 May 9). Alzheimer's Disease Genetics Fact Sheet. Alzheimer’s Disease Education & Referral Center [On-line information]. Available online at http://www.nia.nih.gov/Alzheimers/Publications/geneticsfs.htm through http://www.nia.nih.gov. Accessed May 2009.
Bird, T. (Revised 2008 July 24). Alzheimer Disease Overview. GeneReviews [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene∂=alzheimer through http://www.ncbi.nlm.nih.gov. Accessed May 2009.
Rogaeva, E. (2009 February 5). The Genetic Profile of Alzheimer's Disease: Updates and Considerations. Medscape from Geriatrics and Aging [On-line information]. Available online at http://www.medscape.com/viewarticle/586756 through http://www.medscape.com. Accessed May 2009.
Gandelman, G. (Updated 2008 January 23). Familial dysbetalipoproteinemia. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000402.htm. Accessed May 2009.
Mayo Clinic Staff (2008 September 17). Alzheimer's: Is it in your genes? MayoClinic.com [On-line information]. Available online at http://www.mayoclinic.com/print/alzheimers-genes/AZ00047/METHOD=print through http://www.mayoclinic.com. Accessed May 2009.
(Updated 2008 December). Cardiovascular Disease (Non-traditional Risk Markers) - Risk Markers - CVD (Non-traditional). ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/CardiacDz/CVDRiskMarkerNontrad.html through http://www.arupconsult.com. Accessed May 2009.
(September 18, 2007) Riordan M. Linear association among apoE genotypes with LDL levels and coronary risk. Available online at http://www.theheart.org/article/813529.do through http://www.theheart.org. Accessed July 2009.