© 1995 American Heart Association, Inc.
Articles |
Apoprotein B-100 Production Is Decreased in Subjects Heterozygous for Truncations of Apoprotein B
From the Division of Atherosclerosis, Nutrition and Lipid Research (C.A.A.-S., K.G.P., D.T., J.B., C.Q., G.S.), Washington University School of Medicine, St Louis, Mo; the Resource Facility for Kinetic Analysis (H.R.B.), University of Washington, Seattle; and The Gladstone Foundation Laboratories for Cardiovascular Disease (S.G.Y.), University of California, San Francisco.
Correspondence to Gustav Schonfeld, MD, Washington University School of Medicine, 660 S Euclid, Box 8046, St Louis, MO 63110.
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 
30% rather than
the expected 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.
Key Words: hypobetalipoproteinemia • truncation mutations • apolipoprotein B • kinetics
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