Summary
Hyperapo-β-lipoproteinaemia is a common lipoprotein disorder characterized by an elevated plasma level of the major apolipoprotein, B (apoB) of low-densityβ lipoproteins (LDL), combined with a low ratio of LDL cholesterol to LDL apoB. Hyperapo-β-lipoproteinaemia is due to the overproduction of LDL apoB that results from an enhanced synthesis of very low-density (pre-β) lipoprotein (VLDL) in liver. The plasma levels of high-density (α) lipoprotein (HDL) and its major apolipoprotein, A-I, are often low in hyperapo-β-lipoproteinaemia. Hyperapo-β-lipoproteinaemia is often familial and aggregates in children and adults from families with premature coronary artery disease. The precise defect(s) that cause hyperapo-β-lipoproteinaemia are not known. In a family with premature coronary artery disease and hyperapo-β-lipoproteinaemia, a mutation in codon 4046 in exon 29 of the apolipoprotein B gene, a CGG to TGG transition produced a change from arginine, a positively charged amino acid, to tryptophan, a hydrophobic amino acid, at position 4,019 of the mature apolipoprotein B protein. Decreased incorporation of free fatty acids into triglycerides of adipocytes has been describedin vitro, andin vivo studies suggested a defect in clearance of postprandial lipoproteins associated with decreased uptake of plasma free fatty acids.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Beaty, T. H., Kwiterovich, P. O., Jr., Khoury, M. J., White, S., Bachorik, P. S., Smith, H. H., Teng, B. and Sniderman, A. D. Genetic analysis of plasma sitosterol, apoprotein B and lipoproteins in a large Amish pedigree with sitosterolemia.Am. J. Hum. Genet. 38 (1986) 492–504
Brunzell, J. D., Albers, J. J., Chait, A., Grundy, S., Groszek, E. and McDonald, G. B. Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia.J. Lipid Res. 24 (1983) 147–155
Brunzell, J. D., Sniderman, A., Albers, J. J. and Kwiterovich, P. O., Jr. Apoproteins B and A-1 and coronary artery disease in humans.Arteriosclerosis 4 (1984) 79–83
Chait, A., Albers, J. J. and Brunzell, J. D. Very low density lipoprotein overproduction in genetic forms of hypertriglyceridemia.Eur. J. Clin. Invest. 10 (1980) 17–22
Cianflone, K., Kwiterovich, P. O., Jr., Walsh, M., Forse, A., Rodriguez, M. A. and Sniderman, A. D. Stimulation of fatty acid uptake and triglyceride synthesis in human cultured skin fibroblasts and adipocytes by a serum protein.Biochim. Biophys. Res. Commun. 144 (1987a) 94–100
Cianflone, K. M., Rodriguez, M. A., Walsh, M. J., Vu, H. T., Kwiterovich, P. O. and Sniderman, A. D. Effect of acylation-stimulating protein on triglyceride synthesis in cultured skin fibroblasts from normals and patients with hyperapobetalipoproteinemia.Arteriosclerosis 7 (1987b) 496a
Genest, J., Sniderman, A. D., Cianflone, K., Teng, B., Wacholder, S., Marcel, Y. and Kwiterovich, P. O., Jr. Hyperapobetalipoproteinemia. Plasma lipoprotein responses to oral fat load.Arteriosclerosis 6 (1986) 297–304
Goldstein, J. L. and Brown, M. S. The LDL receptor defect in familial hypercholesterolemia. Implication for pathogenesis and therapy.Med. Clin. N. Am. 66 (1982) 335–362
Goldstein, J. L., Schrott, H. G., Hazzard, W. R., Bierman, E. L. and Motulsky, A. G. Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia.J. Clin. Invest. 52 (1973) 1544–1568
Janus, E. D., Nicoll, A. M., Turner, P. R., Magill, P. and Lewis, B. Kinetic bases of the primary hyperlipidemia: studies of apolipoprotein B turnover in genetically defined subjects.Eur. J. Clin. Invest. 10 (1980) 161–172
Kannel, W. B., Castelli, W. P. and Gordon, T. Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham Study.Ann. Intern. Med. 90 (1979) 85–91
Knott, T. J., Pease, R. J., Powell, L. M., Wallis, S. C., Rall, S. C., Jr., Innerarity, T. L., Blackhart, B., Taylor, W. H., Marcel, Y., Milne, R., Johnson, D., Fuller, M., Lusis, A. J., McCarthy, B. J., Mahley, R. W., Levy-Wilson, B. and Scott, J. Complete protein sequence and identification of structural domains of human apolipoprotein B100.Nature (London) 323 (1986) 734–738
Kwiterovich, P. O., Jr. and Sniderman, A. D. Atherosclerosis and apoproteins B and apoA-I.Prevent. Med. 12 (1983) 815–834
Kwiterovich, P. O., Jr., White, S., Forte, T., Bachorik, P. S., Smith, H. and Sniderman, A. Hyperapo-β-lipoproteinaemia in a kindred with familial combined hyperlipidemia and familial hypercholesterolemia.Arteriosclerosis 7 (1987) 211–225
Kwiterovich, P., Beaty, T., Bachorik, P., Chen, J., Franklin, F., Georgopolous, L. and Sniderman, A. Pediatric hyperlipoproteinemia: The phenotypic expression of hyperapo-β-lipoproteinaemia in young probands and their parents. In Widholm, K. and Naito, H. K. (eds.)Recent Aspects of Diagnosis and Treatment of Lipoprotein Disorders: Impact on the Prevention of Atherosclerotic Disease, Alan R. Liss, Inc., New York, 1988, pp. 89–105
Ladias, J., Kwiterovich, P., Lusis, A., Smith, H. and Antonarkakis, S. A missense mutation arginine4019→ tryptophan in apolipoprotein B in a family with hyperapoB and premature atherosclerosis.Arteriosclerosis 7 (1987) 492a
Sniderman, A., Shapiro, S., Marpole, D., Malcolm, I., Skinner, B. and Kwiterovich, P. O., Jr. The association of coronary atherosclerosis and hyperapo-β-lipoproteinaemia (increased protein but normal cholesterol content in human plasma low density lipoprotein).Proc. Natl. Acad. Sci. (USA) 97 (1980) 604–608
Sniderman, A., Wolfson, C., Teng, B., Franklin, F., Bachorik, P. and Kwiterovich, P. O., Jr. Association of hyperapo-β-lipoproteinaemia with endogenous hypertriglyceridemia and atherosclerosis.Ann. Intern. Med. 97 (1982) 833–839
Sniderman, A. D., Teng, B., Genest, J., Cianflone, K., Wacholder, S. and Kwiterovich, P. O., Jr., Familial aggregation and early expression of hyperapo-β-lipoproteinaemia.Am. J. Cardiol. 55 (1985) 291–295
Sniderman, A., Teng, B., Forse, A., Cianflone, K. and Kwiterovich, P. O., Jr. Depressed glyceride biosynthesis in adipocytes and fibroblasts in hyperapo-β-lipoproteinaemia.Clin. Res. 34 (1986) 668A
Sniderman, A. and Kwiterovich, P. O., Jr. Hyperapo-β-lipoproteinaemia and LDL and HDL2 heterogeneity.Proceedings of the Workshop on Lipoprotein Heterogeneity, U.S. Department of Health and Human Services, NIH Publication No. 87-2646, 1987, pp. 293–304
Teng, B., Thompson, G. R., Sniderman, A. D., Forte, T. M., Krauss, R. M. and Kwiterovich, P. O., Jr. Composition and distribution of low density lipoprotein fractions in hyperapo-β-lipoproteinaemia, normolipidemia and familial hypercholesterolemia.Proc. Natl. Acad. Sci. (USA) 80 (1983) 6662–6666
Teng, B., Sniderman, A. D., Soutar, A. K. and Thompson, G. R. Metabolic basis of hyperapo-β-lipoproteinaemia. Turnover of apolipoprotein B in low density lipoprotein and its precursors and subfractions compared with normal and familial hypercholesterolemia.J. Clin. Invest. 77 (1986) 663–672
Yang, C.-Y., Chen, S-H., Gianturco, S. H., Bradley, W. A., Sparrow, J. T., Tanimura, M., Li, W.-H., Sparrow, D. A., DeLoof, H., Rosseneu, M., Lee, F.-S., Gu, Z.-W., Gotto, A. M., Jr. and Chan, L. Sequence, structure, receptor-binding domains and internal repeats of human apolipoprotein B100.Nature (London) 323 (1986) 738–742
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kwiterovich, P.O. Biochemical, clinical, genetic and metabolic studies of hyperapo-β-lipoproteinaemia. J Inherit Metab Dis 11 (Suppl 1), 57–73 (1988). https://doi.org/10.1007/BF01800571
Issue Date:
DOI: https://doi.org/10.1007/BF01800571