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October 1, 2005Journal of Clinical InvestigationOpen Access

Apoa5 Q139X truncation predisposes to late-onset hyperchylomicronemia due to lipoprotein lipase impairment

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Why the study?

Does the APOA5 Q139X mutation predispose to late-onset hyperchylomicronemia?

Population

Patients with late-onset hyperchylomicronemia (a pedigree and 140 cases) and 200 controls

Comparison

APOA5 Q139X mutation vs Absence of APOA5 Q139X mutation (controls)

Design

Case-control

Authors

CMChristophe Marçais

Discussion

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Overview

Suggests APOA5 Q139X screening in late-onset cases; extends monogenic hyperlipidemia spectrum but remains hypothesis-generating.

Key Points

  • To identify whether mutations in the candidate gene APOA5 cause late-onset, vertically transmitted hyperchylomicronemia and type 5 hyperlipidemia.
  • Sequenced APOA5 in a family pedigree with late-onset hyperchylomicronemia, 200 healthy controls, and 140 unrelated hyperchylomicronemia patients.
  • Performed haplotype mapping, lipoprotein ultracentrifugation, APOB100 in vivo kinetic studies (N=3), and post-heparin lipoprotein lipase mass and activity assays.
  • Identified a heterozygous nonsense mutation (Q139X) in APOA5 in 5 of 9 pedigree carriers and 2 of 140 hyperchylomicronemia cases, while it was absent in 200 controls.
  • Severe hypertriglyceridemia in 8 heterozygous carriers required the presence of a known triglyceride-raising minor APOA5 haplotype on the second allele.
  • Dyslipidemic Q139X carriers exhibited abnormal lipoprotein binding, significantly impaired VLDL catabolism, and marked reductions in lipoprotein lipase activity and mass.

Structured PICO

Does the APOA5 Q139X mutation predispose to late-onset hyperchylomicronemia?

P
Population
Patients with late-onset hyperchylomicronemia (a pedigree and 140 cases) and 200 controls
I
Intervention
APOA5 Q139X mutation
C
Comparator
Absence of APOA5 Q139X mutation (controls)
O
Outcome
Presence of hyperchylomicronemia and lipoprotein lipase impairmentsurrogate

The APOA5 Q139X truncation mutation predisposes to late-onset familial hyperchylomicronemia by impairing lipoprotein lipase activity and VLDL catabolism.

Cite This Study

Christophe Marçais (2005) studied this question.

synapsesocial.com/papers/6a713092fe4101aa97e07907https://doi.org/10.1172/jci24471
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Genetic analysis of a polymorphism in the human apoA-V gene: effect on plasma lipids2003 · 118 citations
  2. 2Genetic variants in Apolipoprotein AV alter triglyceride concentrations in pregnancy.2003 · 18 citations
  3. 3<i>Ex Vivo</i>Measurement of Lipoprotein Lipase-Dependent Very Low Density Lipoprotein (VLDL)-Triglyceride Hydrolysis in Human VLDL: An Alternative to the Postheparin Assay of Lipoprotein Lipase Activity?<sup>1</sup>2001 · 26 citations
  4. 4Plasma Triglyceride Level is a Risk Factor for Cardiovascular Disease Independent of High-Density Lipoprotein Cholesterol Level: A Metaanalysis of Population-Based Prospective Studies1996 · 2,023 citations
  5. 5Metabolic abnormalities of apolipoprotein B‐containing lipoproteins in non‐insulin‐dependent diabetes: a stable isotope kinetic study2000 · 118 citations