Physical Alterations of Plasma Lipoproteins in Tangier Disease and Their Hypothetic Involvement in Pathogenesis

  • Marie-France Dumon
  • Monique Freinex-Clerc
  • Nicole Dousset
  • Quoc Quan Dang
  • Arlette Maret
  • Robert Salvayre
  • Michel Clerc
  • Louis Douste-Blazy
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 150)


Tangier disease is a rare (around 28 cases reported) genetic disorder due to an autosomal recessive gene affecting HDL metabolism (1), characterized by two pathognomonic features: a striking deficiency of plasma HDL in combination with low cholesterol and normal or elevated triglycerides, and extra-lysosomal cholesteryl esters accumulation in histiocytes throughout the body (liver, spleen, lymph nodes, Schwann cells) and mainly in tonsils, intestinal mucosa and cornea (evident only by slit-lamps). In contrast various parenchymal cells (endothelial cells, smooth muscle cells of arteries and veins, hepatocytes) are not affected by the cholesteryl ester storage. In spite of the severe HDL deficiency, Tangier patient seems not affected with a premature atherosclerosis (4), in contrast to the correlation between cardiovascular disease and decreased HDL levels (2, 3). The absence of atherosclerosis in Tangier homozygotes is quite consistent with the lack of cholesterol deposition in the arterial wall.


Fluorescence Quenching Lipid Core Cholesterol Acyl Trans Ferase Lecithin Cholesterol Acyl Transferase Tangier Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    P.N. Herbert, G. Assmann, A.M. Gotto and D.S. Fredrickson. Familial lipoprotein deficiency, in: “Metabolic basis of inherited disease”, J.B. Stanbury et al., eds, Mac Graw Hill, New York, 589–621 (1983).Google Scholar
  2. 2.
    D.P. Barr, E.M. Russ and H.A. Eder. Protein-lipid relationship in human plasma, A. M. J. Med.. 11, 480–492 (1951).Google Scholar
  3. 3.
    G.J. Miller and N.F. Miller. Plasma HDL concentration and development of ischemic heart disease, Lancet 1, 16–20 (1975).Google Scholar
  4. 4.
    F.J. Schaeffer, L.A. Zech, D.E. Schwartz and H.B. Braver. Coronary heart disease prevalence and other clinical features in familial high density lipoprotein deficiency (Tangier disease), Ann. Intern. Med.. 93, 261–266, (1980).Google Scholar
  5. 5.
    G. Assmann, E. Smootz, K. Adler, A. Capurso and K. Oette. The lipoprotein abnormality in Tangier disease, J. Clin. Invest.. 54, 565-575 (1977).Google Scholar
  6. 6.
    L.L. Kay, R. Ronan, E.J. Schaeffer and H.B. Brewer. Tangier disease: a structural defect in apolipoprotein A-l, Proc. Natl. Acad. Sci.. 79, 2485-2489 (1982).Google Scholar
  7. 7.
    A. Rees, J. Stocks, D. Shoulders, L.A. Carlson, F.E. Barelle and D.J. Galton. Restriction enzyme analysis of apolipoprotein A-l gene in fish eye disease, Acta Med. Scand.. 215, 235-237 (1984).Google Scholar
  8. 8.
    V.l. Zannis, A.M. Lees, R.S. Lees and J.L. Breslow. Abnormal apoprotein A I isoprotein composition in Tangier disease, J. Biol. Chem.. 257, 4978-4986 (1982).Google Scholar
  9. 9.
    C. Edelstein, J.I. Gordon, C.A. Vergani, A.L. Catapano, V. Pietrini and A. Scanu. Comparative in vitro study of the pro-apolipoprotein A-l to apolipoprotein A-l converting activity between normal and Tangier plasma. J. Clin. Invest.. 74, 1098–1103 (1984).PubMedCrossRefGoogle Scholar
  10. 10. G. Assmann and E. Smootz. High density lipoprotein infusion and partial plasma exchange in Tangier disease, Eur. J. Clin. Invest.. 8, 131-135 (1978).Google Scholar
  11. 11.
    E.J. Schaeffer, L.L. Lay, L.A. Zech and H.B. Brewer. High density lipoprotein deficiency due to defective metabolism of an abnormal apolipoprotein A-l (apo A-l Tangier), J. Clin. Invest.. 70, 934–935 (1982).CrossRefGoogle Scholar
  12. 12.
    G. Schmitz, H. Robenek and G. Assman. Role of the HDL receptor cycle in macrophage-cholesterol metabolism, E.M.B.O.J.. 4, 613–622 (1985).Google Scholar
  13. 13.
    G. Schmitz, G. Assmann, H. Robenek and B. Brenhausen. Tangier disease: A disorder of intracellular membrane traffic, Proc. Natl. Acad. Sci. U.S.A.. 82, 6305-6309 (1985).Google Scholar
  14. 14.
    M. Rosseneu, G. Assmann, M.J. Taveirne and G. Schmitz. Lipid burding properties of the Tangier apolipoprotein A-l and its isoproteins, J. Lipid Res.. 25, 111-120 (1984).Google Scholar
  15. 15.
    T. Mazzone, C. Lopez and H. Bergstraesser. Modification of very-low density lipoproteins leads to macrophage scavenger receptor uptake and cholesteryl ester deposition, Arteriosclerosis. 7, 191-196 (1987).Google Scholar
  16. 16.
    R.G. Heinen, P.N. Herbert and D.S. Fredrickson. Properties of the plasma VLDL and LDL in Tangier disease, J. Clin. Invest.. 61, 120-132 (1978).Google Scholar
  17. 17.
    P.N. Herbert, J. Forte, R.J. Heinen and D.S. Fredrickson. Tangier disease: one explanation of lipid storage, N. Engl. J. Med.. 299, 519–524, (1978).PubMedCrossRefGoogle Scholar
  18. 18.
    M.F. Dumon, L. Dubourg, T. Jasawant, Y. Anche et M. Clerc. Bilan biochimique et bioclinique d’un nouveau cas de maladie de Tangier, Ann. Biol. Clin.. 43, 681 (1985).Google Scholar
  19. 19.
    R.J. Havel, H.A. Eder and J.H. Bragdon. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. Clin. Invest.. 34, 1345-1353 (1955).Google Scholar
  20. 20.
    M.F. Dumon, S. Visvikis, T. Manabe and M. Clerc. Immunochemical study of the plasma low and high density lipoproteins in Tangier disease, FEB S. letters. 201, 163-167 (1986).Google Scholar
  21. 21.
    Y.L. Marcel, P.K. Weech, T.D. Nguyen, R.W. Milne and W.J. Conathy. Apolipoproteins as the basis for heterogeneity in HDL2 and HDL3, Eur. J. Biochem.. 143, 467-476 (1984).Google Scholar
  22. 22.
    Q.Q. Dang, P. Douste-Blazy, R. Camare and D. Galy, Fluorescence Quenching by iodide ions of low density lipoproteins from normolipidemic and hyperlipidemic type IIa subjects, Chem. Phvs. Lipids. 36, 121-130 (1984).Google Scholar
  23. 23.
    M.I. Grossmann. The quantitative of heparin induced lipemia clearing activity of plasma, J. Lab. Clin. Med.. 43, 445–451 (1954).Google Scholar
  24. 24.
    K.T. Stokke and K.R. Norum. Determination of Lecithin Cholesterol Acyl Trans ferase in human blood plasma, Scan. J. Clin. Lab. Invest.. 27, 21–27 (1971).CrossRefGoogle Scholar
  25. 25.
    M. Clerc, M.F. Dumon, L. Dubourg, T. Jasawant and Y. Anche. Analphalipoproteinemie et risque cardiovasculaire: cas de la maladie de Tangier, Bull. Natl. Acad. Med.. 170, 141-148 (1986).Google Scholar
  26. 26.
    R.A. Davis, G.M. Clinton, R.A. Borchard, M.M. Mc Neal, and G.R. Lattier. Intrahepatic assembly of VLDL: phosphorylation of small molecular weight apo B, J. Biol. Chem.. 259, 3383–3386 (1984).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Marie-France Dumon
    • 1
  • Monique Freinex-Clerc
    • 1
  • Nicole Dousset
    • 2
  • Quoc Quan Dang
    • 2
  • Arlette Maret
    • 2
  • Robert Salvayre
    • 2
  • Michel Clerc
    • 1
  • Louis Douste-Blazy
    • 2
  1. 1.Laboratoire de Biochimie Médicale AUniversité de Bordeaux IIBordeauxFrance
  2. 2.Laboratoire de Biochimie et INSERM U.101, Faculté de MédecineToulouse CedexFrance

Personalised recommendations