Studies on the Protein Defect in Tangier Disease ISOLATION AND CHARACTERIZATION OF AN ABNORMAL HIGH DENSITY LIPOPROTEIN

g/ml) were isolated from the plasma of normal indi-viduals (HDL) and seven homozygous patients with Tangier disease (HDLT). In Tangier patients., the con-centration of protein in the high density region (HDLT) was only 0.5-4.5 % of normal. Immunochemical studies, including mixing experiments conducted in vivo and in vitro, indicated that HDLT was different from HDL. HDLT was the only high density lipoprotein detectable in the plasma of Tangier homozygotes. In heterozygotes both HDL and HDLT were present. HDLT was not de-tected in the plasma of over 300 normal persons and 10 patients with secondary high density lipoprotein deficiency and appeared to be a unique marker for Tan-gier disease. ApoHDL contained two major apoproteins desig-nated apoLp-Gln-I and apoLp-Gln-II; together they comprised 85-90 % of the total protein content. Both of the major HDL apoproteins were present in apoHDLT; but apoLp-Gln-I was disproportionately decreased with respect to apoLp-Gln-II, the ratio of their concentra-tions being 1: 12 in apoHDLT as compared with 3: 1 in apoHDL. Several minor apoprotein components which together comprise 5-15 % of apoHDL were present in approximately normal proportions in apoHDLT. In the HDL of Tangier patients it was estimated that, com-pared with normal individuals, the concentration of apoLp-Gln-I was decreased about 600-fold and the con