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Normal Function
The APOA1 gene provides instructions for making a protein called apolipoprotein A-I (apoA-I). ApoA-I is a component of high-density lipoprotein (HDL). HDL is a molecule that transports cholesterol and certain fats called phospholipids through the bloodstream from the body's tissues to the liver. Once in the liver, cholesterol and phospholipids are redistributed to other tissues or removed from the body.
ApoA-I attaches to cell membranes and promotes the movement of cholesterol and phospholipids from inside the cell to the outer surface. Once outside the cell, these substances combine with apoA-I to form HDL. ApoA-I also triggers a reaction called cholesterol esterification that converts cholesterol to a form that can be fully integrated into HDL and transported through the bloodstream.
HDL is often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. The process of removing excess cholesterol from cells is extremely important for balancing cholesterol levels and maintaining cardiovascular health.
Health Conditions Related to Genetic Changes
Familial HDL deficiency
Mutations in the APOA1 gene cause familial HDL deficiency, an inherited condition characterized by low levels of HDL in the blood and an elevated risk for early-onset cardiovascular disease, which often occurs before age 50. These mutations lead to an altered apoA-I protein. Some versions of the altered protein are less able to promote the removal of cholesterol and phospholipids from cells, which decreases the amount of these substances available to form HDL. Other versions of the altered protein are less able to stimulate cholesterol esterification, which means cholesterol cannot be integrated into HDL particles. Both types of mutation result in low HDL levels. A shortage (deficiency) of HDL is believed to increase the risk of cardiovascular disease.
More About This Health ConditionOther disorders
Mutations in the APOA1 gene can also cause a condition called familial visceral amyloidosis, which is characterized by an abnormal accumulation of proteins (amyloidosis) in internal organs (viscera). The mutations that cause this condition alter the apoA-I protein. Abnormal apoA-I proteins stick together to form amyloid deposits that impair the function of the affected organs. The liver, kidneys, and heart are commonly affected by amyloidosis. Depending on the organs involved, the signs and symptoms of the condition vary. Affected individuals can have an enlarged liver (hepatomegaly), chronic kidney disease, or a form of heart disease called cardiomyopathy. However, in some people, the condition is very mild and causes no apparent signs or symptoms.
Other Names for This Gene
- apo-AI
- apoA-I
- APOA1_HUMAN
- apolipoprotein A-I
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Batal R, Tremblay M, Krimbou L, Mamer O, Davignon J, Genest J Jr, Cohn JS. Familial HDL deficiency characterized by hypercatabolism of mature apoA-I but not proapoA-I. Arterioscler Thromb Vasc Biol. 1998 Apr;18(4):655-64. doi: 10.1161/01.atv.18.4.655. Citation on PubMed
- Chambenoit O, Hamon Y, Marguet D, Rigneault H, Rosseneu M, Chimini G. Specific docking of apolipoprotein A-I at the cell surface requires a functional ABCA1 transporter. J Biol Chem. 2001 Mar 30;276(13):9955-60. doi: 10.1074/jbc.M010265200. Epub 2001 Jan 9. Citation on PubMed
- Chroni A, Liu T, Gorshkova I, Kan HY, Uehara Y, Von Eckardstein A, Zannis VI. The central helices of ApoA-I can promote ATP-binding cassette transporter A1 (ABCA1)-mediated lipid efflux. Amino acid residues 220-231 of the wild-type ApoA-I are required for lipid efflux in vitro and high density lipoprotein formation in vivo. J Biol Chem. 2003 Feb 28;278(9):6719-30. doi: 10.1074/jbc.M205232200. Epub 2002 Dec 17. Citation on PubMed
- Daum U, Leren TP, Langer C, Chirazi A, Cullen P, Pritchard PH, Assmann G, von Eckardstein A. Multiple dysfunctions of two apolipoprotein A-I variants, apoA-I(R160L)Oslo and apoA-I(P165R), that are associated with hypoalphalipoproteinemia in heterozygous carriers. J Lipid Res. 1999 Mar;40(3):486-94. Citation on PubMed
- Eriksson M, Schonland S, Yumlu S, Hegenbart U, von Hutten H, Gioeva Z, Lohse P, Buttner J, Schmidt H, Rocken C. Hereditary apolipoprotein AI-associated amyloidosis in surgical pathology specimens: identification of three novel mutations in the APOA1 gene. J Mol Diagn. 2009 May;11(3):257-62. doi: 10.2353/jmoldx.2009.080161. Epub 2009 Mar 26. Citation on PubMed or Free article on PubMed Central
- Oram JF. HDL apolipoproteins and ABCA1: partners in the removal of excess cellular cholesterol. Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):720-7. doi: 10.1161/01.ATV.0000054662.44688.9A. Epub 2003 Jan 9. Citation on PubMed
- Rowczenio D, Dogan A, Theis JD, Vrana JA, Lachmann HJ, Wechalekar AD, Gilbertson JA, Hunt T, Gibbs SD, Sattianayagam PT, Pinney JH, Hawkins PN, Gillmore JD. Amyloidogenicity and clinical phenotype associated with five novel mutations in apolipoprotein A-I. Am J Pathol. 2011 Oct;179(4):1978-87. doi: 10.1016/j.ajpath.2011.06.024. Epub 2011 Aug 5. Citation on PubMed or Free article on PubMed Central
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.