TY - JOUR
T1 - A new apolipoprotein B truncation (apo B-43.7) in familial hypobetalipoproteinemia
T2 - Genetic and metabolic studies
AU - Srivastava, Neelam
AU - Noto, Davide
AU - Averna, Maurizio
AU - Pulai, Judit
AU - Srivastava, Rai Ajit K.
AU - Cole, Thomas G.
AU - Latour, Mickey A.
AU - Patterson, Bruce W.
AU - Schonfeld, Gustav
N1 - Funding Information:
From the Division of Atherosclerosis, Nutrition and LipM Research, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO. Subm#ted February 8, 1996; accepted May 7, 1996. Supported in part by National Institutes of Health Grant No. HLRO142460, General Clinical Research Center Grant No. USPHS MO1RRO0036, and Diabetes Research Training Center Grant No. NIH5P60DK20579. Address reprint requests to Gustav Schonfeld, MD, MO 63110. Copyright © 1996 by W.B. Saunders Company 0026-0495/96/4510-0018503.00/0
PY - 1996
Y1 - 1996
N2 - 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 · 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 12.0 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 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.
AB - 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 · 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 12.0 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 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.
UR - http://www.scopus.com/inward/record.url?scp=0029820885&partnerID=8YFLogxK
U2 - 10.1016/S0026-0495(96)90251-6
DO - 10.1016/S0026-0495(96)90251-6
M3 - Article
C2 - 8843188
AN - SCOPUS:0029820885
VL - 45
SP - 1296
EP - 1304
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
SN - 0026-0495
IS - 10
ER -