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

The South African population harbors genes that are derived from varying de grees 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 hy percholesterolemia (FH) phenotype in the recently founded Coloured populati on 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 m utation causing familial defective apolipoprotein B-100 (FDB) and seven low -density lipoprotein receptor LDLR gene defects known to be relatively comm on in South Africans with FH. Six founder-type 'South African mutations' we re responsible for FH in similar to 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 g enetic evidence that Caucasoid admixture contributes significantly to the a pparently 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 adm ixture in populations with different disease risks.