Familial hypercholesterolemia

Familial hypercholesterolemia (FH) is seen in the general population at a frequency of 1 in 200 to 1 in 500. However, it is seen much more often among Afrikaners in South Africa, Christian Lebanese, and French Canadians.^[1]  Estimated disease frequencies in some of these populations are as high as 1 in 70.^[2]

Some genetic diseases occur more frequently in populations that are isolated geographically or culturally due to founder effects.  A founder effect is the reduction in genetic variation that occurs when a colony is formed from a small subset of a larger population.  When a small colony separates from a larger population, the frequency of gene variants that are present may be very different from the original population ^[3].  As the colony grows over time from these common ancestors, we are more likely to see these variants in their offspring.  If these genetic variants cause disease, then we will see the disease more commonly in populations that arose from a founder event.

While these frequencies do not tell us how the original mutation occurred, they can help to explain the history of familial hypercholesterolemia (FH).  For example, researchers have identified an FH gene change in Afrikaners that was traced back to a single family from the Netherlands that immigrated to South Africa in the 1600s.  As a result of this founder event, this single genetic change (mutation) causes most of the cases of FH seen in the Afrikaner population ^[2].