Summary
Familial hypercholesterolemia (FH), at a prevalence of more than 1 in 100, is at least five times more common in one South African population group than in populations in North America and Europe. Fourteen homozygotic tamilial hypercholesterolemic subjects from this South African group were genotyped for two intragenic DNA restriction fragment length polymorphisms (RFLPs) in the LDL-receptor gene. A Stu I polymorphism is located in exon 8, and a Pvu II polymorphism, in intron 15. Of ten unrelated FH homozygotes genotyped for both RFLPs, nine were homozygous for an S+P- haplotype, and one was heterozygous for an S+P-/S-P+ heplotype. The remaining four were genotyped for Pvu II only and were homozygous for P-. Compared with a previously determined population frequency for the latter, this represents an association (P<0.05) between the frequency for the P- allele and FH in this population, and this finding is consistent with the “founder gene effect” previously postulated to be present on genealogical and biochemical evidence.
Similar content being viewed by others
References
Botha MC, Beighton P (1983) Inherited disorders in the Afrikaner population of Southern Africa. S Afr Med J 64:609–612
Botha MC, Pritchard J (1972) Blood group gene frequencies: an indication of the genetic constitution of population samples in Cape Town. S Afr Med J [Suppl] 46:1–27
Brink PA, Steyn LT, Bester AJ, Steyn K (1986) Linkage disequilibrium between a marker on the LDL receptor and high cholesterol. S Afr Med J 70:80–82
Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232:34–47
Church GM, Gilbert W (1984) Genomic sequencing. Proc Natl Acad Sci USA 81:1991–1995
Dean G (1972) The porphyrias 2nd edn. Pitman, London
Goldstein JL, Brown MS (1984) Familial hypercholesterolemia. In: Stanbury JW, Wyngaarden JB, Frederickson DS (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 672–712
Heese JA (1972) Die herkoms van die Afrikaner. Balkema, Cape Town, p 39
Hobbs HH, Lehrman MA, Yamamoto T, Russell DW (1985) Polymorphism and evolution of Alu sequences in the human low density lipoprotein receptor gene. Proc Natl Acad Sci USA 82:7651–7655
Humphries SE, Horsthemke B, Seed M, Holm M, Wynn V, Kesseling AM, Donald JA, Jowett N, Galton DJ, Williamson R (1985) A common DNA polymorphism of the low density lipoprotein (LDL) receptor gene and its use in diagnosis. Lancet I:1003–1005
Jenkins T, Nicholls E, Gordon E, Mendelsohn D, Seftel HC, Andrew MJA (1980) Familial hypercholesterolaemia—a common genetic disorder in the Afrikaans speaking population. S Afr Med J 57: 943–947
Jooste PL, Benade AJS, Rossouw JE (1986) Prevalence of familial hypercholesterolaemia in three rural South African communities. S Afr Med J 69:548–551
Kotze MJ, Retief AE, Brink PA, Weich HFH (1986) A DNA polymorphism in the human low-density lipoprotein receptor gene. S Afr Med J 70:77–79
Maniatis T, Fritsch EF, Sambrook J (eds) (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Schneider WJ, Brown MS, Goldstein JL (1983) Kinetic defects in the processing of the low density receptor in fibroblasts from WHHL rabbits and a family with familial hypercholesterolaemia. Mol Biol Med 1:353
Seftel HC, Baker SG, Sandler MP, Forman MB, Joffe BI, Mendelsohn D, Jenkins T, Mieny CJ (1980) A host of hypercholesterolaemic homozygotes in South Africa. Br Med J 281:623–636
Spoelstra B (1963) The “Doppers” in South Africa, 1760–1899. Nasionale Boekhandel, Cape Town
Theal GMcG (1922) History of Southern Africa, vol 4. Struik, Cape Town, p 351
Torrington M, Botha JL, Pilcher GJ, Baker SG (1984) Association between familial hypercholesterolaemia and church affiliation: is this the result of sociocultural isolation of migrant farmers in 19th-century South Africa? S Afr Med J 65:762–767
Vandenplas S, Wiid I, Grobler-Rabie A, Brebner K, Ricketts M, Bester AJ, Boyd C, Mathew C (1984) Blot hybridization analysis of genomic DNA. J Med Genet 21:164–172
Van der Westhuyzen DR, Coetzee GA, Demasius IPC, Harley EH, Gevers W, Baker SG, Seftel HC (1984) Low density receptor mutations in South African homozygous familial hypercholesterolemic patients. Arteriosclerosis 4:238–247
Wahl GM, Stern M, Stark GR (1979) Efficient transfer of large DNA fragments from agarose gel to diabnylomethyl-paper and rapid hybridization by using dextran sulphate. Proc Natl Acad Sci USA 76:3683–3687
Wyndham CH (1978) Ischaemic heart disease mortality rates in White South Africans compared with other populations. S Afr Med J 54: 596–601
Yamamoto T, Davis CG, Brown MS, Schneider WJ, Casey ML, Goldstein JL, Russell DW (1984) The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell 39:27–38
Yamamoto T, Bishop RW, Brown MS, Goldstein JL, Russell DW (1986) Deletion in cysteine-rich region of LDL receptor impedes transport to cell surface in WHHL rabbit. Science 232:1230–1237
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Brink, P.A., Steyn, L.T., Coetzee, G.A. et al. Familial hypercholesterolemia in South African Afrikaners. Hum Genet 77, 32–35 (1987). https://doi.org/10.1007/BF00284709
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00284709