UP-REGULATED SYNTHESIS OF BOTH APOLIPOPROTEIN-A-I AND APOLIPOPROTEIN-B IN FAMILIAL HYPERALPHALIPOPROTEINEMIA AND HYPERBETALIPOPROTEINEMIA

A family was identified with vertical transmission through three gener ations with simultaneous increases of apolipoprotein A-I (apoA-I), apo lipoprotein B (apoB), low-density lipoprotein (LDL)-cholesterol, and h igh-density lipoprotein (HDL)-cholesterol, which we have designated fa milial hyperalphalipoproteinemia and hyperbetalipoproteinemia (HA/HBL) . Affected patients develop xanthomas and coronary artery disease (CAD ). HA/HBL apoA-I and LDL-apoB were isolated and characterized. The in vivo kinetics of radiolabeled apoA-I and LDL-apoB were evaluated in tw o HA/HBL probands and three controls. Structural and metabolic charact erization showed normal apoA-I and LDL-apoB. The kinetics of metabolis m of HA/HBL apoA-I in the HA/HBL subjects showed that elevated apoA-I levels were solely due to an increased synthesis rate (15.2 to 17.6 mg /kg/d v 11.1 to 11.4 mg/kg/d) with a normal apoA-I residence time in p lasma (4.2 to 5.4 days v 5.1 to 5.3 days). The elevation of LDL-apoB l evels resulted from both an increased synthetic rate (16.6 to 22.9 mg/ kg/d v 12.3 to 13.8 mg/kg/d) and a prolonged residence time (3.3 to 3. 8 days v 1.4 to 1.9 days). In addition, we evaluated another HA/HBL pr oband of an unrelated family with HA/HBL to confirm the kinetic data. LDL-receptor binding studies of HA/HBL fibroblasts showed normal bindi ng, uptake, and degradation of LDL isolated from a normolipemic contro l. The serum concentration of the cholesterol ester transfer protein ( CETP) was normal in the studied probands. An apoB 3500 and apoB 3531 m utant, respectively, was ruled out by polymerase chain reaction (PCR), In conclusion, the site of the molecular defect in HA/HBL subjects ma y be involved in the coordinate regulation of metabolism for both LDL and HDL. Copyright (C) 1998 by W.B. Saunders Company.