title: Upregulated synthesis of both apolipoprotein A-I and apolipoprotein B in familial hyperalphalipoproteinemia and hyperbetalipoproteinemia.
abstract: A family was identified with vertical transmission through three generations with simultaneous increases of apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol, which we have designated familial 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 two HA/HBL probands and three controls. Structural and metabolic characterization showed normal apoA-I and LDL-apoB. The kinetics of metabolism 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 plasma (4.2 to 5.4 days v 5.1 to 5.3 days). The elevation of LDL-apoB levels 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 proband of an unrelated family with HA/HBL to confirm the kinetic data. LDL-receptor binding studies of HA/HBL fibroblasts showed normal binding, uptake, and degradation of LDL isolated from a normolipemic control. The serum concentration of the cholesterol ester transfer protein (CETP) was normal in the studied probands. An apoB 3500 and apoB 3531 mutant, respectively, was ruled out by polymerase chain reaction (PCR). In conclusion, the site of the molecular defect in HA/HBL subjects may be involved in the coordinate regulation of metabolism for both LDL and HDL.
authors.affiliation: Medizinische Hochschule Hannover, Abteilung für Gastroenterologie und Hepatologie, Germany.
authors.forename: H H
authors.initials: HH
authors.lastname: Schmidt
authors.forename: R E
authors.initials: RE
authors.lastname: Gregg
authors.forename: U J
authors.initials: UJ
authors.lastname: Tietge
authors.forename: U
authors.initials: U
authors.lastname: Beisiegel
authors.forename: L A
authors.initials: LA
authors.lastname: Zech
authors.forename: H B
authors.initials: HB
authors.lastname: Brewer
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
authors.forename: D
authors.initials: D
authors.lastname: Bojanovski
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000096:biosynthesis*; D001055:Apolipoproteins B / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D003327:Coronary Disease / Q000209:etiology; D005260:Female; D006023:Glycoproteins; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D006951:Hyperlipoproteinemias / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins