Familial hypercholesterolemia in South African Afrikaners. PvuII and StuI DNA polymorphisms in the LDL-receptor gene consistent with a predominating founder gene effect.

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 familial hypercholesterolemic subjects from this South African group were genotyped for two intragenic DNA restriction fragment length polymorphisms (RFLPs) in the LDL-receptor gene. A StuI polymorphism is located in exon 8, and a PvuII 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 + haplotype. The remaining four were genotyped for PvuII only and were homozygous for P-. Compared with a previously determined population frequency for the latter, this represents an association (P less than 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.

Linkage disequilibrium between a marker on the low-density lipoprotein receptor and high cholesterol levels.

We describe the presence of a linkage disequilibrium between high cholesterol levels in Afrikaner individuals and the common allele of the Pvu II restriction fragment polymorphism on the low-density lipoprotein (LDL) receptor gene. The frequencies of the common and the rare allele in a sample of the Afrikaner population were 0.654 and 0.346 (65 individuals) and 0.794 and 0.206 in the hypercholesterolaemic population (34 patients) (P less than 0.05). This finding supports other evidence for a founder origin of the high frequency of familial hypercholesterolaemia among Afrikaners.