Background: Accuracy of clinical diagnosis of heterozygotes with familial hypercholesterolemia (FH) is limited. The aim of our study was to demonstrate possibilities of progressive diagnostic approach, DNA analysis, LDL receptor gene (LDLR) and apolipoprotein B (ApoB) in case of our study, and compare our results with the data obtained in other populations.
Methods and results: The low density lipoprotein receptor (LDLR) gene RFLP frequencies for restriction endonucleases AvaII, HincII, NcoI, PvuII and StuI were determined in the sample of 52 FH patients and in the group of 37 healthy individuals. Using PCR, the LDLR gene was then tested for Pro664-Leu and Val408-Met point mutations. The first DNA diagnosis of familial defective apolipoprotein B-100 (FDB) using point mutation PCR analysis of 26. exon of ApoB gene in Czech Republic was performed. LDLR gene RFLP frequencies for restriction endonucleases AvaII, HincII, NcoI, PvuII and StuI in he sample of 52 FH patients were 0.48, 0.52, 0.73, 0.31 and 0.93 respectively. LDLR gene RFLP frequencies for enzymes AvaII, HincII, NcoI, PvuII and StuI in the group of 37 healthy individuals were 0.39, 0.50, 0.70, 0.22 and 0.99 respectively. In the group of FH patients no point mutations Pro664-Leu and Val408-Met were detected. However, there was found 110bp insertion in the 9th exon of LDLR gene in two FH patients during studies of Val408-Leu mutation. Two FDB probands in the FH group and another 7 FDB individuals in probands families were detected. FDB frequency in the sample of FH patients was 3.8%.
Conclusions: LDLR gene RFLP frequencies and FDB frequency in our group of FH patients did not differ from that of FH patients in other Caucasian populations. DNA analysis is advantageous complementary method for diagnosis of FH and is irreplaceable for the detection of FDB.