Tangier disease: a structural defect in apolipoprotein A-I (apoA-I Tangier).

Open Access
Publisher Website
Google Scholar
Abstract
Tangier disease is a familial disorder characterized by orange tonsils, cholesterol ester deposition in reticuloendothelial cells, abnormal chylomicron remnants, and a marked reduction in high density lipoproteins. Plasma concentrations of the apolipoproteins ApoA-I and apoA-II in patients with Tangier disease are .apprx. 1% and 7% of those in normal subjects, respectively. Previous studies have shown that the low plasma concentrations of apoA-I and apoA-II are due to increased fractional catabolism with a relatively normal apoA-I and apoA-II synthesis. Plasma apoA-I and apoA-II were isolated to electrophoretic homogeneity from delipidated plasma lipoproteins from a patient with Tangier disease. ApoA-ITangier differed from apoA-I from control subjects in amino acid composition, electrophoretic mobility, apparent MW on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and heterogeneity of isoforms on isoelectric focusing. ApoA-IITangier, however, appeared to be identical to normal apoA-II in amino acid composition and in immunological as well as chemical properties. These results were interpreted as indicating that apoA-ITangier has a different covalent structure than does normal apoA-I, and apoA-IITangier is identical to normal apoA-II. This structural change in apoA-ITangier is associated with rapid catabolism of apoA-ITangier- and apoA-IITangier-containing plasma lipoproteins, and it leads to the deficiency in high density lipoproteins, abnormal chylomicron remnants, and the intracellular accumulation of cholesterol ester characteristic of Tangier disease.