Lipoprotein metabolism in an apoB-80 familial hypobetalipoproteinemia heterozygote

Amanda J Hooper; Ken Robertson; Danie Champain; Jianmin Hua; Swithin Song; Klaus G Parhofer; P Hugh R Barrett; Frank M van Bockxmeer; John R Burnett

doi:10.1016/j.clinbiochem.2016.02.008

Lipoprotein metabolism in an apoB-80 familial hypobetalipoproteinemia heterozygote

Clin Biochem. 2016 Jun;49(9):720-722. doi: 10.1016/j.clinbiochem.2016.02.008. Epub 2016 Feb 23.

Authors

Amanda J Hooper¹, Ken Robertson², Danie Champain³, Jianmin Hua⁴, Swithin Song⁴, Klaus G Parhofer⁵, P Hugh R Barrett³, Frank M van Bockxmeer⁶, John R Burnett⁷

Affiliations

¹ Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Australia.
² Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Australia.
³ School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia.
⁴ Department of Radiology, Royal Perth Hospital, Perth, Australia.
⁵ Medical Department II, Grosshadern, University of Munich, Munich, Germany.
⁶ Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Australia; School of Surgery, University of Western Australia, Crawley, Australia.
⁷ Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia. Electronic address: john.burnett@health.wa.gov.au.

PMID: 26916057
DOI: 10.1016/j.clinbiochem.2016.02.008

Abstract

Objective: Familial hypobetalipoproteinemia (FHBL) is characterized by mutations in APOB, the majority of these causing protein truncations, and low plasma levels of apolipoprotein (apo) B. The hypobetalipoproteinemia may be due to enhanced clearance and possibly reduced production of apoB-containing lipoproteins; the mechanism may depend on the length of the apoB truncation. We studied fasting lipoprotein metabolism in an FHBL subject heterozygous for a mutation causing a truncated apoB, apoB-80.

Design and methods: Very low density lipoprotein (VLDL)-, intermediate density lipoprotein (IDL)-, and low density lipoprotein (LDL)-apoB kinetics were determined in the fasting state using stable isotope methods and compartmental modeling.

Results: Compared with lean normolipidemic controls the apoB-80 FHBL subject had an elevated VLDL-apoB fractional catabolic rate and lower LDL production. ApoB production rates and IDL- and LDL-apoB fractional catabolic rates were not different.

Conclusion: FHBL subjects heterozygous for a mutation truncating apoB to 80% of full-length are able to produce VLDL-apoB normally, but have rapid clearance of these particles, resulting in low levels of circulating apoB.

Keywords: Apolipoprotein B; Compartmental modeling; Familial hypobetalipoproteinemia; Kinetics; Lipoprotein; Metabolism.

Publication types

Comparative Study

MeSH terms

Adult
Apolipoprotein B-100 / blood*
Biomarkers / blood*
Case-Control Studies
Female
Follow-Up Studies
Genetic Predisposition to Disease
Heterozygote
Humans
Hypobetalipoproteinemias / blood*
Hypobetalipoproteinemias / genetics*
Kinetics
Lipids / analysis
Lipoproteins, VLDL / metabolism*
Male
Mutation / genetics*
Prognosis
Young Adult

Substances

APOB protein, human
Apolipoprotein B-100
Biomarkers
Lipids
Lipoproteins, VLDL