Characteristics of 46 heterozygous carriers and 57 unaffected relatives in five Danish families with familial defective apolipoprotein B-100

Plasma concentrations of cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) B, and lipoprotein(a) (Lp[a]) in 46 persons heterozygous for the apo B-3500 mutation causing familial defective apo B-100 (FDB) were compared with those in 57 non-FDB relatives. FDB patients had 50% to 70% higher mean concentrations of cholesterol, LDL cholesterol, and apo B than non-FDB relatives (P < 10(-4) for all three variables). Triglycerides were higher (P = .016) and HDL cholesterol was lower (P = .021) in FDB patients. The concentration ranges of these variables were broad in each family, and there was no between-family difference in means for cholesterol and LDL cholesterol. There was no phenotype-specific difference in Lp(a) concentrations between FDB patients and non-FDB relatives. Apo E4 is normally associated with higher concentrations of LDL and apo E2 with lower concentrations. This relation was partly reversed in FDB patients: apo E4 was associated with lower apo B concentrations and apo E2 with higher apo B concentrations. Tendon xanthomata were found in members of two of the five families. Six of 12 FDB patients > 50 years old had atherosclerotic disease. In contrast, all 18 non-FDB relatives > 50 years old were apparently healthy. A total of 8 FDB patients with atherosclerotic disease had 36% higher cholesterol concentrations, 28% higher apo B concentrations, 50% higher triglyceride concentrations, and 120% higher Lp(a) concentrations than FDB patients without clinical atherosclerosis.