title: Variations on a gene: rare and common variants in ABCA1 and their impact on HDL cholesterol levels and atherosclerosis.
abstract: Cholesterol and its metabolites play a variety of essential roles in living systems. Virtually all animal cells require cholesterol, which they acquire through synthesis or uptake, but only the liver can degrade cholesterol. The ABCA1 gene product regulates the rate-controlling step in the removal of cellular cholesterol: the efflux of cellular cholesterol and phospholipids to an apolipoprotein acceptor. Mutations in ABCA1, as seen in Tangier disease, result in accumulation of cellular cholesterol, reduced plasma high-density lipoprotein cholesterol, and increased risk for coronary artery disease. To date, more than 100 coding variants have been identified in ABCA1, and these variants result in a broad spectrum of biochemical and clinical phenotypes. Here we review genetic variation in ABCA1 and its critical role in cholesterol metabolism and atherosclerosis in the general population.
authors.affiliation: Center for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, V6T 1Z4 British Columbia.
authors.forename: Liam R
authors.initials: LR
authors.lastname: Brunham
authors.forename: Roshni R
authors.initials: RR
authors.lastname: Singaraja
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood*; D014644:Genetic Variation; D006801:Humans; D007009:Hypolipoproteinemias / Q000235:genetics* / Q000378:metabolism; D009154:Mutation
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D002784:Cholesterol