The entire amino acid sequence of Tangier preproapoA-I has been determined. The sequence of Tangier preproapoA-I was identical to normal preproapoA-I except for a single base substitution (G leads to T) which resulted in the isosteric replacement of a glutamic acid residue at position 120 to aspartic acid. Results indicate the rapid rate of catabolism of apoA-I in Tangier disease is due to a post-translational defect in apoA-I metabolism rather than a structural defective apoA-I. Human liver apoB-100 cDNA has been isolated in a Lambdagt-11 expression library. The apoB-100 mRNA is 15-18 kb enough to encode a protein of M.W. 400 kd. Computer analysis of nucleic acid derived amino acid sequence of cloned apoB-100 cDNA predict a significant portion of the protein is organized into Beta-structure which may be important in lipid apoB-100 interactions in LDL and contributed to the insolubility of delipidated apoB-100 in aqueous buffers. In collaboration with S. Naylor and associates, we have localized the apoB-100 gene to the p23 leads to pter region of chromosome 2. The cloning of human apoB-100, has provided new insights into the structural and physicochemical properties of apoB-100, and enable studies to be initiated on the factors modulating apoB-100 biosynthesis and the apoB-100 gene in patients with dyslipoproteinemias. Two additional apolipoproteins, C-III and E have been cloned. ApoE gene expression in culture monocyte-macrophages derived from normal subject and apoE deficient patient was evaluated. Cellular apoE mRNA level was greatly reduced. Furthermore no major deletion or insertions were detectable in the apoE gene in the E deficient patient. Thus the deficiency of plasma apoE in the patient with apoE deficiency is due to markedly decreased level of apoE mRNA and decreased synthesis of the E apolipoprotein.