Summary
We found an increased prevalence of an Sst-1 restriction fragment length polymorphism (RFLP), localized to the apolipoprotein C-III gene, in lipid clinic patients with diverse hyperlipidaemic phenotypes. Studies on a normolipidaemic control population confirmed previous reports of differing frequencies of the RFLP in different racial groups. Reexamination of the patient data, taking into account racial composition, provided further support for an association of the Sst-1 RFLP with primary hypercholesterolaemia, type III hyperlipoproteinaemia, as well as with hypertriglyceridaemia as had previously been observed. These results suggest that the Sst-1 site is linked to a gene defect with a minor or subtle phenotypic effect which enhances the expression of a co-existent major monogenic defect of lipoprotein transport.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Beaumont JL, Carlson LA, Cooper GR, Fejfar Z, Frederickson DS, Strasser T (1970) Classification of hyperlipidaemias and hyperlipoproteinaemias. Bull WHO 43:891–915
Beighton P (1976) Genetic disorders in Southern Africa. S Afr Med J 50:1125–1128
Berger GMB, Abraham PR (1977) Selective protamine sulphate inactivation of lipoprotein lipase and hepatic lipase in human post-heparin plasma: specific lipase levels in normal and in type I hyperlipoproteinaemia. Clin Chim Acta 81:219–228
Botha MC, Beighton P (1983) Inherited disorders in the Afrikaner population of Southern Africa. S Afr Med J 64:609–612
Brown MS, Goldstein JL, Fredrickson DS (1983) Familial type III hyperlipoproteinaemia. (Dysketa lipoproteinaemia). In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease. 5th edn. (McGraw-Hill, New York), pp 655–671
Coetzee GA, Van der Westhuizen DR, Berger GMB, Henderson HE, Gevers W (1982) Low density lipoprotein metabolism in cultured fibroblasts from a new group of patients presenting clinically with homozygous familial hypercholesterolaemia. Arteriosclerosis 2:303–311
Ferns GAA, Stocks J, Ritchie C, Galton DJ (1985) Genetic polymorphisms of apolipoprotein C-III and insulin in survivors of myocardial infarction. Lancet II:300–303
Ferns GAA, Stocks J, Galton DJ (1986) C-III DNA restriction fragment length polymorphism and myocardial infarction. Lancet I:94
Fleis JL (1981) Statistical methods for rates and proportions. Wiley, New York, pp 1–301
Goldstein JL, Schrott HG, Hazzard WR, Berman EL, Motulsky AG (1973) Hyperlipidaemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and combined hyperlipidaemia. J Clin Invest 52:1544–1568
Hatch FT, Lees RS (1968) Practical methods for plasma lipoprotein analysis. Adv Lipid Res 6:1–68
Janus ED, Nicoll AM, Turner PR, Magill P, Lewis B (1980) Kinetic basis of the primary hyperlipidemias: studies of apolipoprotein B turnover in genetically undefined subjects. Eur J Clin Invest 10:161–172
Karathanesis SK, Zannis VI, Breslow JL (1983) Linkage of human apoprotein A-I and C-III. Nature 304:371–373
Kessling AM, Horsthemke B, Humphries SE (1985) A study of DNA polymorphisms around the human apolipoprotein A-I gene in hyperlipidaemic and normal individuals. Clin Genet 28:296–306
Morris SW, Price WH (1985) DNA sequence polymorphisms in the apolipoprotein A-I/C-III gene cluster. Lancet II:1127–1128
Ordovas JM, Schaefer EJ, Salem D, Ward RH, Glueck CJ, Vergani C, Wilson PWF, Karathanasis SK (1986) Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinaemia. N Engl J Med 314:671–677
Poncz M, Solowiejezyk D, Horpel B, Morey Y, Schwartz E, Surrey S (1982) Construction of human gene libraries from small amounts of peripheral blood; analysis of β-like globin genes. Hemoglobin 6:27–36
Rees A, Shoulders CC, Stocks J, Galton DJ, Baralle FE (1983) DNA polymorphism adjacent to human apoprotein A-I gene: relation to hypertriglyceridaemia. Lancet II:444–446
Rees A, Stocks J, Sharpe CR, Vella MA, Shoulders CC, Katz J, Jowett NI, Barelle FE, Galton DJ (1985) Deoxyribonucleic acid polymorphism in the apolipoprotein A-I/C-III gene cluster. J Clin Invest 76:1090–1095
Rifkind BM, Segal P (1983) Lipid research clinics. Program reference values for hyperlipidaemia and hypolipidaemia. JAMA 250:1869–1872
Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517
Sprecher DL, Taam L, Brewer HB Jr (1984) Two-dimensional electrophoresis of human plasma apolipoproteins. Clin Chem 30:2084–2092
Vella M, Kessling A, Jowett N, Rees A, Stocks J, Wallis S, Galton DJ (1985) DNA polymorphism flanking the apo A-I and insulin genes and type III hyperlipidaemia. Hum Genet 69:275–276
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Henderson, H.E., Landon, S.V., Michie, J. et al. Association of a DNA polymorphism in the apolipoprotein C-III gene with diverse hyperlipidaemic phenotypes. Hum Genet 75, 62–65 (1987). https://doi.org/10.1007/BF00273841
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00273841