A NEW APOLIPOPROTEIN-B TRUNCATION (APO B-43.7) IN FAMILIAL HYPOBETALIPOPROTEINEMIA - GENETIC AND METABOLIC STUDIES

We describe a new truncation of apolipoprotein (apo) B in a white kind red with familial hypobetalipoproteinemia (FHBL), Apo B-43.7, found in a daughter and her father, was due to a C --> T change in base positi on 6162 of the apo B gene converting the arginine (residue 1986) codon CGA to a stop codon TGA. Both subjects were heterozygotes, and both a po 8-43.7- and apo B-100-containing particles were present in plasma. On density gradient ultracentrifugation (DGUC), approximately 30% to 4 0% of apo B-43.7 floated with very-low-density lipoprotein (VLDL)/inte rmediate-density lipoprotein (IDL)-density particles and 60% to 70% fl oated with high-density lipoprotein (HDL)-density particles. To assess the metabolism of apo B, C-13-leucine was infused and its rates of ap pearance in and disappearance from apo B-43.7- and apo B-100-containin g particles were quantified by multicompartmental kinetic analysis. Ap o B-100 entered plasma via VLDL with a production rate of 30 mg . kg(- 1). d(-1). Fractional catabolic rates (FCRs) for apo B-100 VLDL, IDL, and low-density lipoprotein (LDL) were 20.0, 16.0, and 0.46 pools . d( -1), respectively. The production rate of apo B-43.7 was 9.6 mg . kg(- 1). d(-1), and FCRs for apo B-43.7 VLDL- and HDL-like particles were 1 2.0 and 1.8 pools . d(-1), respectively. Approximately 30% of apo B-43 .7 in HDL-density particles was derived from VLDL apo B-43.7, and abou t 70% appeared to enter the plasma as HDLs. The relatively low product ion rate of apo B-43.7 is compatible with previous reports that apo B truncations are produced at lower rates than their apo B-100 counterpa rts. Copyright (C) 1996 by W.B. Saunders Company