Founder mutations in the LDL receptor gene contribute significantly to the familial hypercholesterolemia phenotype in the indigenous South African population of mixed ancestry

Authors: Loubser, Odell; Marais, A David; Kotze2, Maritha J¹; Godenir, Nicole²; Thiart2, Rochelle¹; Scholtz2, Charlotte L¹; de Villiers2, J Nico P¹; Hillermann2, Renate¹; Firth, Jean C³; Weich, Hellmuth Fh⁴; Maritz, Frans⁴; Jones2, Sheena³; van der Westhuyzen, Deneys R

Source: Clinical Genetics, Volume 55, Number 5, May 1999 , pp. 340-345(6)

Publisher: Blackwell Publishing

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Abstract:

The South African population harbors genes that are derived from varying degrees of admixture between indigenous groups and immigrants from Europe and the East. This study represents the first direct mutation-based attempt to determine the impact of admixture from other gene pools on the familial hypercholesterolemia (FH) phenotype in the recently founded Coloured population of South Africa, a people of mixed ancestry. A cohort of 236 apparently unrelated patients with clinical features of FH was screened for a common mutation causing familial defective apolipoprotein B-100 (FDB) and seven low-density lipoprotein receptor (LDLR) gene defects known to be relatively common in South Africans with FH. Six founder-type `South African mutations' were responsible for FH in ∼20% of the study population, while only 1 patient tested positive for the familial defective apolipoprotein B-100 mutation R3500Q. The detection of multiple founder-type LDLR gene mutations originating from European, Indian and Jewish populations provides direct genetic evidence that Caucasoid admixture contributes significantly to the apparently high prevalence of FH in South African patients of mixed ancestry. This study contributes to our knowledge of the biological history of this unique population and illustrates the potential consequences of recent admixture in populations with different disease risks.

Keywords: admixture; familial hypercholesterolemia; indigenous population; low density lipoprotein receptor; mutational origin

Document Type: Research article

DOI: 10.1034/j.1399-0004.1999.550507.x

Affiliations: 1: Division of Human Genetics, Faculty of Medicine, University of Stellenbosch, Tygerberg, 2: MRC/UCT Research Unit for Cell Biology of Atherosclerosis, Department of Medical Biochemistry, University of Cape Town, Cape Town, 3: Department of Medicine, University of Cape Town, Cape Town, 4: Lipid Clinic, Cardiac Unit, Department of Internal Medicine, University of Stellenbosch and Tygerberg Hospital, Tygerberg, South Africa

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