Familial defective apolipoprotein B-100: a lesson from homozygous and heterozygous patients

Familial defective apolipoprotein B-100 (FDB) is a genetic disorder caused by a substitution of glutamine for arginine at residue 3500 of the apolipop rotein B-100 molecule. We have identified 23 heterozygotes and one homozygo te for FDB (frequency 1:20) in a group of 510 patients with hypercholestero lemia. Mean age of the patients (18 females and 6 males) was 46 years. The diagnosis of FDB was based on point mutation PCR analysis of exon 26 of the apo B gene. Plasma lipids in heterozygous patients were: total cholesterol 8.76+/-1.2 mmol/l, triglycerides 1.42+/-0.5 mmol/l, HDL-cholesterol 1.43+/ -0.3 mmol/l, LDL-cholesterol 6.69+/-1.2 mmol/l, apoB 1.69+/-0.4 g/l, Lp(a) 0.26+/-0.2 g/l. The most frequent apoE genotype was 3/3 (19 patients), apoE 3/4 genotype was found in 3 patients and one person had apoE 2/3. Xanthela sma palpebrarum was present in 4 patients and tendon xanthomas in 3 patient s including the homozygote. Premature manifestation of coronary heart disea se was revealed in 3 patients. Sixteen patients were treated with statins, a combination of statin and resin was used in 2 patients (including the hom ozygote), whereas six patients were treated with the diet only, We conclude that although the plasma lipid levels of total and LDL cholesterol in FDB patients are lower than in patients with familial hypercholesterolemia, the patients with FDB suffer from premature atherosclerosis. The therapeutic a pproach to FDB individuals and patients with familial hypercholesterolemia is very similar.