Background. Familial defective apolipoprotein (apo) B-100 (FDB) is a common inherited metabolic disorder. Reduced binding of the apo B-100, the major protein of LDL particles, to LDL receptor results in marked hypercholesterolemia. FDB is caused particularly by an arginine to glutamine substitution at the codon for amino acid 3500 of the apo B-100. The aim of this study was to determine mutations potentially responsible for hypercholesterolemia in the apo B gene and to estimate their frequency in the group of Czech hyperlipidemic patients. Methods and Results. The groups of 169 unrelated patients with primary isolated hypercholesterolemia (total cholesterol > 6,5 mmol/l, triglycerides < 2,3 mmol/l) and 58 unrelated patients with combined hyperlipoproteinemia (total cholesterol > 6,5 mmol/l, triglycerides > 2,3 mmol/l) were screened for mutations in codon 3500 region of the apolipoprotein B gene by denaturing gradient gel electrophoresis. Mutation R3500Q was detected in 20 patients with isolated hypercholesterolemia (11,8 %) and in 2 patients with combined hyperlipoproteinemia (3,4 %). No other mutations were found. Conclusion. The frequency of FDB in our group of patients with primary isolated hypercholesterolemia is high when compared with data published in other countries. We suggest that all patients with primary isolated hypercho- lesterolemia (total cholesterol > 6,5 mmol/l) in the Czech Republic should be analysed for the presence of mutation R3500Q in the apo B gene.

        Key words: familial defective apolipoprotein B-100 (FDB), hypercholesterolemia, hyperlipoproteinemia, athe- rosclerosis, mutation, denaturing gradient gel electrophoresis (DGGE).