ESTIMATION OF THE PREVALENCE OF FAMILIAL HYPERCHOLESTEROLEMIA IN A RURAL AFRIKANER COMMUNITY BY DIRECT SCREENING FOR 3 AFRIKANER FOUNDER LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE-MUTATIONS

We have determined the prevalence of familial hypercholesterolaemia (F H) in a rural Afrikaner community by means of direct DNA screening for three founder-related Afrikaner low density lipoprotein (LDL) recepto r gene mutations. A random sample of 1612 persons, aged 15-64 years, w as selected as a subsample of 4583 subjects from an Afrikaner communit y living in the southwestern Cape, South Africa. Participants who had a total serum cholesterol (TC) in the high TC category as defined in t he consensus recommendations by the Southern African Heart Foundation, were screened for three founder-related LDL receptor gene mutations, causing FH in 90% of Afrikaners. Of the subsample, 201 participants (1 2.5%) had TC levels above the 80th percentile. In this group the combi ned prevalence of the three common Afrikaner LDL receptor gene defects (D206E, FH Afrikaner-1; V408M, FH Afrikaner-2; D154N, FH Afrikaner-3) was calculated as 1:83. When taking into account the reported backgro und prevalence of other FH gene defects of 1:500 in this community, th eir overall prevalence of FH was estimated to be 1:72. The significant differences found between the FH patients and other high risk patient s with raised cholesterol levels were higher TC and LDL cholesterol le vels and lower high density lipoprotein cholesterol levels in FH patie nts. The treatment status of the molecularly identified FH patients an d other hypercholesterolaemic persons suggests that this condition is inadequately diagnosed and poorly managed in this study population. An extrapolation to the entire South African population suggests that th ere are about 112000 FH patients in the country who are underdiagnosed as a group and therefore not receiving the care that would help to re duce the burden of FH-associated ischaemic heart disease in South Afri ca.