Abstract
Epidemiological studies have identified elevated low density lipoprotein (LDL)1–3 and diminished high density lipoprotein (HDL) cholesterol levels3,4 as risk factors for coronary artery disease. The major protein component of HDL is apoprotein A-I (apo A-I), a polypeptide of 243 amino acids of known primary amino acid sequence5. This apoprotein serves as a cofactor for the plasma lecithin-cholesterol acyltransferase (LCAT) enzyme responsible for the formation of most cholesteryl esters in plasma, and also promotes cholesterol efflux from cells6,7. The primary translation product of apo A-I contains both a pre and a pro segment8, and post-translational processing of apo A-I may be involved in the formation of the functional plasma apo A-I isoproteins9,10. Defective apo A-I processing may be the underlying problem in Tangier disease11, in which patients have low plasma HDL and apo A-I levels despite normal apo A-I synthesis12,13. Patients have been reported with conditions distinct from Tangier disease in whom severe deficiency or absence of apo A-I has been associated with very low HDL levels and severe coronary artery disease14,15. We have now examined the apo A-I gene in two such patients and their first degree relatives. These patients have been reported to have skin and tendon xanthomas, corneal clouding and severe premature coronary atherosclerosis associated with very low HDL levels and deficiencies of two apoproteins, apo A-I and apo C-III15. We show that both probands are homozygous for a defect in the apo A-I gene locus.
Similar content being viewed by others
References
Kannel, W. B., Castelli, W. P., Gordon, T. & McNamara, P. M. Ann. intern. Med. 74, 1–12 (1971).
Marx, J. L. Science 194, 711–714 (1976).
Kannel, W. B., Castelli, W. P. & Gordon, T. Ann. intern. Med. 90, 85–91 (1979).
Castelli, W. P. et al. Circulation 55, 767–772 (1977).
Brewer, H. B. Jr, et al. Biochem. biophys. Res. Commun. 80, 623–630 (1978).
Fielding, C. J., Shore, V. G. & Fielding, P. D. Biochem. biophys. Res. Commun. 46, 1943–1949 (1972).
Jackson, R. L., Gotto, A. M., Stein, O. & Stein, Y. J. biol. Chem. 250, 7204–7209 (1975).
Gordon, J. I. et al. J. biol. Chem. 257, 971–978 (1982).
Zannis, V. I., Breslow, J. L., SanGiacomo, T. R., Aden, D. P. & Knowles, B. B. Biochemistry 20, 7089–7096 (1981).
Zannis, V. I., Kurnit, D. & Breslow, J. L. J. biol. Chem. 257, 536–544 (1982).
Zannis, V. I., Lees, A. M., Lees, R. S. & Breslow, J. L. J. biol. Chem. 257, 4978–4986 (1982).
Assmann, G., Capurso, A., Smootz, E. & Wellner, U. Atherosclerosis 30, 321–332 (1978).
Glickman, R. M., Green, P. H., Lees, R. S. & Tall, A. New Engl. J. Med. 299, 1424–1427 (1978).
Schaefer, E. J., Heaton, W. H., Wetzel, M. G. & Brewer, H. B. Jr, Arteriosclerosis 2, 16–26 (1982).
Norum, R. A. et al. New Engl. J. Med. 306, 1513–1519 (1982).
Breslow, J. L. et al. Proc. natn. Acad. Sci. U.S.A. 79, 6861–6865 (1982).
Southern, E. M. J. molec. Biol. 98, 503–517 (1975).
Shoulders, C. C. & Baralle, F. E. Nucleic Acids Res. 10, 4873–4882 (1982).
Kan, Y. W. & Dozy, A. M. Lancet ii, 910–912 (1978).
Maniatis, T. et al. Cell 15, 687–701 (1978).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Karathanasis, S., Norum, R., Zannis, V. et al. An inherited polymorphism in the human apolipoprotein A-I gene locus related to the development of atherosclerosis. Nature 301, 718–720 (1983). https://doi.org/10.1038/301718a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/301718a0
- Springer Nature Limited
This article is cited by
-
An association analysis between ApoA1 polymorphisms and the high-density lipoprotein (HDL) cholesterol level and myocardial infarction (MI) in Japanese
Journal of Human Genetics (2004)
-
Hypercholesterolemia in five Israeli Christian-Arab kindreds is caused by the ?Lebanese? allele at the low density lipoprotein receptor gene locus and by an additional independent major factor
Human Genetics (1991)