The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway

The ABC1 transporter was identified as the defect in Tangier disease by a c ombined strategy of gene expression microarray analysis, genetic mapping, a nd biochemical studies. Patients with Tangier disease have a defect in cell ular cholesterol removal, which results in near zero plasma levels of HDL a nd in massive tissue deposition of cholesteryl esters. Blocking the express ion or activity of ABC1 reduces apolipoprotein-mediated lipid efflux from c ultured cells, and increasing expression of ABC1 enhances it. ABC1 expressi on is induced by cholesterol loading and cAMP treatment and is reduced upon subsequent cholesterol removal by apolipoproteins. The protein is incorpor ated into the plasma membrane in proportion to its level of expression. Dif ferent mutations were detected in the ABC1 gene of 3 unrelated patients. Th us, ABC1 has the properties of a key protein in the cellular lipid removal pathway, as emphasized by the consequences of its defect in patients with T angier disease.