Familial defective apolipoprotein B-100 (FDB) is caused by a single G-to-A substitution at nucleotide 10,708 leading to an arginine to glutamine change at amino acid 3,500 of the apolipoprotein B-100 and thus, a reduced binding of the apolipoprotein B to the low density lipoprotein (LDL) receptor. In the present study, the prevalence of FDB in Switzerland was estimated, on the one hand, from a sample of 728 healthy volunteers whose origin was spread out over the entire German, French, and Romansh speaking parts of the country, and, on the other hand, from 142 unrelated Swiss families with primary hypercholesterolemia comprising 520 individuals. Using polymerase chain reaction (PCR)-based methods, three individuals were identified with the point mutation in the sample of volunteers, equivalent to a prevalence of approximately 1/240 (90% confidence interval: 1.51 x 10(-3)-1.03 x 10(-2)). The frequency of FDB in the sample of hypercholesterolemic subjects was 7/142, yielding a prevalence of approximately 1/190 extrapolated to the general population (90% confidence interval: 2.63 x 10(-3)-9.17 x 10(-2)). The combined prevalence based on both samples was 1/209. Thus, the investigated point mutation was highly prevalent in Switzerland and appeared to be more frequent than in other populations studied hitherto. Furthermore, the presence of the mutation was not necessarily associated with an elevation of serum cholesterol levels, particularly in young individuals. While in the non-affected volunteers cholesterol levels increased between the age of 19 and 23 years by 0.22 mmol/l or by 5.6% (P = 0.001), this phenomenon was even more pronounced in individuals with FDB. The three volunteers with the point mutation demonstrated an increase in total cholesterol concentrations by 1.30 mmol/l or by 25% within 2 years, suggesting that, in the early twenties, cholesterol concentrations increase markedly from normal to elevated levels. Considering the estimated high prevalence and the relative ease of PCR-based tests, screening for FDB may become a standard procedure in patients with suggested familial forms of hypercholesterolemia.