PHENOTYPIC-EXPRESSION AND FREQUENCY OF FAMILIAL DEFECTIVE APOLIPOPROTEIN B-100 IN BELGIAN HYPERCHOLESTEROLEMICS

DNA screening for apolipoprotein (ape) B mutations causing familial de fective apolipoprotein B-100 (FDB) was performed in 87 hyperlipidemic Belgian individuals using heteroduplex analysis. Eighteen FDB heterozy gotes from 5 unrelated families were identified. Three of the index ca ses reported an early family history of premature coronary heart disea se (CHD). The frequency of the apo B-3500 mutation was 8% in Belgians with type IIa hyperlipidemia, indicating that the prevalence of FDB ma y be as high as 1 in 250 in the general Belgian population. Plasma lip id levels of the patients identified in the present study are similar to those previously reported for FDB heterozygotes. We compared these data with results obtained in a genotype/phenotype correlation study o f heterozygous familial hypercholesterolemia (FH) in the Afrikaner pop ulation of South Africa. Plasma cholesterol levels in FDB heterozygote s were similar to those reported for FH heterozygotes with defective r eceptors (Asp(206) --> Glu, approximate to 20% normal receptor activit y), but significantly lower than in FH heterozygotes with a mutant pro tein which virtually lacks receptor activity (Val(408) --> Met, < 2% n ormal receptor activity). FDB appears to be a significant genetic caus e of hypercholesterolemia in Belgium.