title: Apoprotein B-100 production is decreased in subjects heterozygous for truncations of apoprotein B.
abstract: Among individuals who are heterozygous for familial hypobetalipoproteinemia (FHBL) and who have various truncations of apoprotein (apo) B (ie, FHBL with apoB truncation/apoB-100 genotypes), the plasma concentrations of apoB-100 are typically approximately 30% rather than the expected approximately 50% of those in unaffected family members. The metabolic basis for the low apoB-100 levels is unknown. Therefore, we compared the metabolism of apoB-100 in 8 subjects with heterozygous FHBL (2 apoB-89/apoB-100, 2 apoB-75/apoB-100, 2 apoB-54.8/apoB-100, 1 apoB-52/apoB-100, and 1 apoB-31/apoB-100) with the metabolism of apoB-100 in 8 apoB-100/apoB-100 control subjects who were paired with the heterozygotes by gender, age, height, weight, and race. Endogenous labeling of apoB-100 with [13C]leucine and a multicompartmental kinetic model were used to obtain kinetic parameters. FHBL heterozygotes had significantly reduced VLDL apoB-100 production rates (7.7 +/- 3.7 versus 21.2 +/- 6.2 mg.kg-1.d-1, P = .002) and LDL apoB-100 production rates (4.5 +/- 3.12 versus 15.3 +/- 1 mg.kg-1.d-1, P = .05) compared with control subjects. Fractional conversion rates of VLDL to LDL were not significantly different (0.67 +/- 0.36 versus 0.77 +/- 0.17 pools/d), and the respective fractional catabolic rates of apoB-100 in VLDL, IDL, and LDL also were similar in both groups. Thus, FHBL heterozygotes produced apoB-100 at about 30% of the rates of control subjects. We believe these reduced production rates largely account for the lower than expected levels of apoB-100 and LDL cholesterol in the plasma of FHBL heterozygotes.
authors.affiliation: Division of Atherosclerosis, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Aguilar-Salinas
authors.forename: P H
authors.initials: PH
authors.lastname: Barrett
authors.forename: K G
authors.initials: KG
authors.lastname: Parhofer
authors.forename: S G
authors.initials: SG
authors.lastname: Young
authors.forename: D
authors.initials: D
authors.lastname: Tessereau
authors.forename: J
authors.initials: J
authors.lastname: Bateman
authors.forename: C
authors.initials: C
authors.lastname: Quinn
authors.forename: G
authors.initials: G
authors.lastname: Schonfeld
mesh_terms: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008297:Male
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008055:Lipids