ATP Binding Cassette A1 Transporter Function and Tangier Disease

  • Ernst J. Schaefer
  • H. Bryan Brewer


The ATP binding cassette A1 (ABCA1) transporter facilitates the efflux of free cholesterol and phospholipid onto high density lipoprotein (HDL) particles, mainly very small discoidal precursor HDL particles, known as prebeta 1 HDL. Once these particles pick up these lipids, they are converted to small discoidal alpha 4 migrating HDL and with cholesterol esterification mature into larger spherical alpha 3 and 2 HDL particles. Separate chapters in this book are devoted to HDL particle metabolism. Patients with Tangier Disease, named after the Chesapeake Bay island home of the first two cases described, have marked HDL deficiency, moderate hypertriglyceridemia, and low density lipoprotein (LDL) cholesterol levels that are about 50% of normal values. The only HDL particle detectable in the plasma of homozygotes is the very small precursor prebeta 1 HDL particle, which in these patients is rapidly catabolized by the kidneys. Homozygotes have lipid laden macrophages in their tonsils, spleen, liver, arterial wall, other tissues, and Schwann cells, which can result in enlarged orange tonsils, hepatosplenomegaly, premature coronary heart disease (CHD), and neuropathy. Their LDL is about 50% of normal, is smaller and more triglyceride enriched than normal LDL, and its protein component is cleared from plasma at twice the normal fractional rate. Heterozygotes with this disease have about 50% of normal HDL cholesterol, lack large alpha 1 HDL, and have an increased risk of premature CHD when compared to control subjects. Findings in this disease underscore the importance of ABCA1 in promoting free cholesterol efflux from a variety of cells and maintaining cellular cholesterol homeostasis.


High Density Lipoprotein Cholesteryl Ester Beta Carotene High Density Lipoprotein Particle Premature Coronary Heart Disease 
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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Tufts UniversityBostonUSA

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