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 kindred with familial hypobetalipoproteinemia (FHBL). Apo B-43.7, found in a daughter and her father, was due to a C --> T change in base position 6162 of the apo B gene converting the arginine (residue 1986) codon CGA to a stop codon TGA. Both subjects were heterozygotes, and both apo B-43.7- and apo B-100-containing particles were present in plasma. On density gradient ultracentrifugation (DGUC), approximately 30% to 40% of apo B-43.7 floated with very-low-density lipoprotein (VLDL)/intermediate-density lipoprotein (IDL)-density particles and 60% to 70% floated with high-density lipoprotein (HDL)-density particles. To assess the metabolism of apo B, 13C-leucine was infused and its rates of appearance in and disappearance from apo B-43.7- and apo B-100-containing particles were quantified by multicompartmental kinetic analysis. Apo B-100 entered plasma via VLDL with a production rate of 30 mg x kg-1 x 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 x d-1, respectively. The production rate of apo B-43.7 was 9.6 mg x kg-1 x d-1, and FCRs for apo B-43.7 VLDL- and HDL-like particles were 12.0 and 1.8 pools x d-1, respectively. Approximately 30% of apo B-43.7 in HDL-density particles was derived from VLDL apo B-43.7, and about 70% appeared to enter the plasma as HDLs. The relatively low production 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 counterparts.
Srivastava
N
N
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Noto
D
D
Averna
M
M
Pulai
J
J
Srivastava
R A
RA
Cole
T G
TG
Latour
M A
MA
Patterson
B W
BW
Schonfeld
G
G
D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000032:analysis / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood* / Q000235:genetics*; D008074:Lipoproteins / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008074:Lipoproteins