Frequency of the R3500Q mutation of the apolipoprotein B-100 gene in a sample screened clinically for familial hypercholesterolemia in Hungary.

Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) cause early onset of coronary heart diseases (CHD). According to the recommendations of the international MEDPED program, we tried to find FH cases. We analyzed 73 FH probands and their 304 first-degree relatives. A total of 39 probands were found from the 21000 subjects screened (1:538) from family doctors' registers recording all citizens, while the remaining 34 were derived from screened patients from lipid clinics. In our FH probands, four cases of FDB (R3500Q mutation) were diagnosed with allele-specific PCR, and the mutation was also detectable in five cases out of seven living family members. In the remaining 69 FH families, 156 people were diagnosed clinically with FH, and 31.8% of the males (against 13% of the not clinically diagnosed FH males, P<0.01), and 32.4% of the females (against 13.5% of the not clinically diagnosed FH females, P<0.01) suffered from early onset CHD. The plasma total cholesterol level of the FDB patients, especially in the younger patients, was very close to normal values. Therefore, the FDB patients seem to be under-represented in this type of survey. Because FDB is one of the independent causes of early onset CHD, the R3500Q mutation should be considered in families with a high frequency of cardiovascular diseases.