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. 1980 Nov;66(5):892–900. doi: 10.1172/JCI109956

A-IMilano apoprotein. Decreased high density lipoprotein cholesterol levels with significant lipoprotein modifications and without clinical atherosclerosis in an Italian family.

G Franceschini, C R Sirtori, A Capurso 2nd, K H Weisgraber, R W Mahley
PMCID: PMC371523  PMID: 7430351

Abstract

Significant hypertriglyceridemia with a very marked decrease of high density lipoproteins (HDL)-cholesterol levels (7-14 mg/dl) was detected in three members (father, son, and daughter) of an Italian family. The three affected individuals did not show any clinical signs of atherosclerosis, nor was the atherosclerotic disease significantly present in the family. Lipoprotein lipase and lecithin:cholesterol acyltransferase activites were normal or slightly reduced. Morphological and compositional studies of HDL in the subjects showed a significant enlargement of the lipoprotein particles (approximately 120 vs. approximately 94 A for control HDL) and a concomitant increase in the triglyceride content. Analytical isoelectric focusing of HDL apoproteins provided evidence for multiple isoproteins in the apoprotein(apo)-A-I range, with nine different bands being detected instead of the usual four bands observed in normal subjects. Two-dimensional immunoelectrophoresis against apo-A antiserum indicated a clear reduction of apo-A in the alpha electrophoretic region, with splitting of the protein "peak." The observation in otherwise clinically healthy subjects of hypertriglyceridemia, reduced HDL-cholesterol, and marked apoprotein abnormalities, without a significant incidence of atherosclerotic disease in the family suggests this is a new disease entity in the field of lipoprotein pathology, very probably related to an altered amino acid composition of the apo-A-I protein (see Weisgraber et al. 1980. J. Clin. Invest. 66: 901-907).

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Assmann G., Herbert P. N., Fredrickson D. S., Forte T. Isolation and characterization of an abnormal high density lipoprotein in Tangier Diesase. J Clin Invest. 1977 Jul;60(1):242–252. doi: 10.1172/JCI108761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Assmann G., Simantke O., Schaefer H. E., Smootz E. Characterization of high density lipoproteins in patients heterozygous for Tangier disease. J Clin Invest. 1977 Nov;60(5):1025–1035. doi: 10.1172/JCI108853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Assmann G., Smootz E., Adler K., Capurso A., Oette K. The lipoprotein abnormality in Tangier disease: quantitation of A apoproteins. J Clin Invest. 1977 Mar;59(3):565–575. doi: 10.1172/JCI108672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BURSTEIN M., SAMAILLE J. [On a rapid determination of the cholesterol bound to the serum alpha- and beta-lipoproteins]. Clin Chim Acta. 1960 Jul;5:609–609. doi: 10.1016/0009-8981(60)90075-9. [DOI] [PubMed] [Google Scholar]
  5. Boberg J., Boberg M., Gross R., Grundy S., Augustin J., Brown V. The effect of treatment with clofibrate on hepatic triglyceride and lipoprotein lipase activities of post heparin plasma in male patients with hyperlipoproteinemia. Atherosclerosis. 1977 Aug;27(4):499–503. doi: 10.1016/0021-9150(77)90168-x. [DOI] [PubMed] [Google Scholar]
  6. Boberg J. Heparin-released blood plasma lipoprotein lipase activity in patients with hyperlipoproteinemia. Acta Med Scand. 1972 Jan-Feb;191(1-2):97–102. [PubMed] [Google Scholar]
  7. Brown W. V., Levy R. I., Fredrickson D. S. Studies of the proteins in human plasma very low density lipoproteins. J Biol Chem. 1969 Oct 25;244(20):5687–5694. [PubMed] [Google Scholar]
  8. Carlson L. A., Philipson B. Fish-eye disease. A new familial condition with massive corneal opacities and dyslipoproteinaemia. Lancet. 1979 Nov 3;2(8149):922–924. [PubMed] [Google Scholar]
  9. Clifton-Bligh P., Nestel P. J., Whyte H. M. Tangier disease. Report of a case and studies of lipid metabolism. N Engl J Med. 1972 Mar 16;286(11):567–571. doi: 10.1056/NEJM197203162861103. [DOI] [PubMed] [Google Scholar]
  10. DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
  11. Ferrans V. J., Fredrickson D. S. The pathology of Tangier disease. A light and electron microscopic study. Am J Pathol. 1975 Jan;78(1):101–158. [PMC free article] [PubMed] [Google Scholar]
  12. Glickman R. M., Green P. H., Lees R. S., Tall A. Apoprotein A-I synthesis in normal intestinal mucosa and in Tangier disease. N Engl J Med. 1978 Dec 28;299(26):1424–1427. doi: 10.1056/NEJM197812282992602. [DOI] [PubMed] [Google Scholar]
  13. Glickman R. M., Green P. H. The intestine as a source of apolipoprotein A1. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2569–2573. doi: 10.1073/pnas.74.6.2569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Glomset J. A. Physiological role of lecithin-cholesterol acyltransferase. Am J Clin Nutr. 1970 Aug;23(8):1129–1136. doi: 10.1093/ajcn/23.8.1129. [DOI] [PubMed] [Google Scholar]
  15. Glueck C. J., Fallat R. W., Millett F., Gartside P., Elston R. C., Go R. C. Familial hyper-alpha-lipoproteinemia: studies in eighteen kindreds. Metabolism. 1975 Nov;24(11):1243–1265. doi: 10.1016/0026-0495(75)90063-3. [DOI] [PubMed] [Google Scholar]
  16. Gordon T., Castelli W. P., Hjortland M. C., Kannel W. B., Dawber T. R. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977 May;62(5):707–714. doi: 10.1016/0002-9343(77)90874-9. [DOI] [PubMed] [Google Scholar]
  17. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Heinen R. J., Herbert P. N., Fredrickson D. S. Properties of the plasma very low and low density lipoproteins in Tangier disease. J Clin Invest. 1978 Jan;61(1):120–132. doi: 10.1172/JCI108910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Herbert P. N., Henderson L. O. Plasma-triglycerides do not regulate high-density lipoprotein concentrations. Lancet. 1979 Jun 30;1(8131):1368–1370. doi: 10.1016/s0140-6736(79)92007-5. [DOI] [PubMed] [Google Scholar]
  20. Kashyap M. L., Srivastava L. S., Chen C. Y., Perisutti C. G., Campbell M., Lutmer R. F., Glueck C. J. Radioimmunoassay of human apolipoprotein CII. A study in normal and hypertriglyceridemic subjects. J Clin Invest. 1977 Jul;60(1):171–180. doi: 10.1172/JCI108753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Laurell C. B. Electroimmuno assay. Scand J Clin Lab Invest Suppl. 1972;124:21–37. doi: 10.3109/00365517209102748. [DOI] [PubMed] [Google Scholar]
  22. Malik N., Berrie A. New stain fixative for proteins separated by gel isoelectric focusing based on Coomassie Brilliant Blue. Anal Biochem. 1972 Sep;49(1):173–176. doi: 10.1016/0003-2697(72)90255-2. [DOI] [PubMed] [Google Scholar]
  23. Miller G. J., Miller N. E. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet. 1975 Jan 4;1(7897):16–19. doi: 10.1016/s0140-6736(75)92376-4. [DOI] [PubMed] [Google Scholar]
  24. Miller N. E., Weinstein D. B., Carew T. E., Koschinsky T., Steinberg D. Interaction between high density and low density lipoproteins uptake and degradation by cultured human fibroblasts. J Clin Invest. 1977 Jul;60(1):78–88. doi: 10.1172/JCI108772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Naito H. K., Wada M., Ehrhart L. A., Lewis L. A. Polyacrylamide-gel disc-electrophoresis as a screening procedure for serum lipoprotein abnormalities. Clin Chem. 1973 Feb;19(2):228–234. [PubMed] [Google Scholar]
  26. Noble R. P., Campbell F. M. Improved accuracy in automated fluorometric determination of plasma triglycerides. Clin Chem. 1970 Mar;16(3):166–170. [PubMed] [Google Scholar]
  27. Noble R. P. Electrophoretic separation of plasma lipoproteins in agarose gel. J Lipid Res. 1968 Nov;9(6):693–700. [PubMed] [Google Scholar]
  28. Patsch W., Sailer S., Braunsteiner H. An enzymatic method for the determination of the initial rate of cholesterol esterification in human plasma. J Lipid Res. 1976 Mar;17(2):182–185. [PubMed] [Google Scholar]
  29. Rouser G., Fkeischer S., Yamamoto A. Two dimensional then layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids. 1970 May;5(5):494–496. doi: 10.1007/BF02531316. [DOI] [PubMed] [Google Scholar]
  30. Rössner S., Kjellin K. G., Mettinger K. L., Sidén A., Söderström C. E. Normal serum-cholesterol but low H.D.L.-cholesterol concentration in young patients with ischaemic cerebrovascular disease. Lancet. 1978 Mar 18;1(8064):577–579. doi: 10.1016/s0140-6736(78)91026-7. [DOI] [PubMed] [Google Scholar]
  31. Schaefer E. J., Blum C. B., Levy R. I., Jenkins L. L., Alaupovic P., Foster D. M., Brewer H. B., Jr Metabolism of high-density lipoprotein apolipoproteins in Tangier disease. N Engl J Med. 1978 Oct 26;299(17):905–910. doi: 10.1056/NEJM197810262991701. [DOI] [PubMed] [Google Scholar]
  32. Scherer R., Ruhenstroth-Bauer G. Untersuchung der Lecithin-Cholesterin-Acyltransferase-Aktivität im Serum von drei Patienten mit Tangier-Krankheit (Hyp-alpha-Lipoproteinämie. Klin Wochenschr. 1973 Nov;21(1):1059–1061. doi: 10.1007/BF01468319. [DOI] [PubMed] [Google Scholar]
  33. Sirtori C. R., Tremoli E., Sirtori M., Conti F., Paoletti R. Treatment of hypertriglyceridemia with metformin. Effectiveness and analỳsis of results. Atherosclerosis. 1977 Apr;26(4):583–592. doi: 10.1016/0021-9150(77)90125-3. [DOI] [PubMed] [Google Scholar]
  34. Stange E., Agostini B., Paenberg J. Changes in rabbit lipoprotein properties by dietary cholesterol, and saturated and polyunsaturated fats. Atherosclerosis. 1975 Jul-Aug;22(1):125–148. doi: 10.1016/0021-9150(75)90073-8. [DOI] [PubMed] [Google Scholar]
  35. Stein Y., Glangeaud M. C., Fainaru M., Stein O. The removal of cholesterol from aortic smooth muscle cells in culture and Landschutz ascites cells by fractions of human high-density apolipoprotein. Biochim Biophys Acta. 1975 Jan 24;380(1):106–118. doi: 10.1016/0005-2760(75)90049-1. [DOI] [PubMed] [Google Scholar]
  36. Streja D., Steiner G., Kwiterovich P. O., Jr Plasma high-density lipoproteins and ischemic heart disease: studies in a large kindred with familial hypercholesterolemia. Ann Intern Med. 1978 Dec;89(6):871–880. doi: 10.7326/0003-4819-89-6-871. [DOI] [PubMed] [Google Scholar]
  37. Vessby B., Boberg J., Lithell H. Lipolytic activities in post-heparin plasma in man measured with different substrate emulsions. Clin Sci Mol Med. 1978 Feb;54(2):201–203. doi: 10.1042/cs0540201. [DOI] [PubMed] [Google Scholar]
  38. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]

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