Increased production of apolipoprotein A-I associated with elevated plasma levels of high-density lipoproteins, apolipoprotein A-I, and lipoprotein A-I in a patient with familial hyperalphalipoproteinemia

Daniel J. Rader, Juergen R. Schaefer, Peter Lohse, Katsunori Ikewaki, Fairwell Thomas, William A. Harris, Loren A. Zech, Carlos A. Dujovne, H. Bryan Brewer

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Familial hyperalphalipoproteinemia (FHA) is a heritable trait associated with elevated plasma concentrations of high-density lipoprotein (HDL) cholesterol and possibly with longevity and protection against coronary heart disease (CHD). The metabolic basis and molecular etiology of FHA have not been established in most kindreds. The proband of a kindred with FHA and possible longevity was found to have elevated plasma levels of HDL cholesterol, apolipoprotein (apo) A-I, and lipoproteins containing apo A-I without apo A-II (Lp A-I), but normal levels of apo A-II and lipoproteins containing apo A-I with apo A-II (Lp A-I:A-II). The in vivo kinetics of apo A-I and apo A-II were studied in the FHA proband and in control subjects using both exogenous radiotracer (125I-apo A-I and 131I-apo A-II) and endogenous stable isotope (primed constant infusion of 13C6-phenylalanine) labeling techniques. The production rate (PR) of apo A-I was markedly increased in the FHA subject (28.9 mg/kg · d) compared with the control subjects (12.0 ± 2.1 mg/kg · d), whereas the apo A-II PR was not substantially increased. The primary sequence of the proband's apo A-I gene, including 1.2 kb of the 5′-flanking sequence, was normal. We conclude that a selective upregulation of apo A-I production is one metabolic cause of FHA, and results in high plasma concentrations of HDL cholesterol, apo A-I, and Lp A-I and possibly in protection from atherosclerotic CHD.

Original languageEnglish (US)
Pages (from-to)1429-1434
Number of pages6
JournalMetabolism
Volume42
Issue number11
DOIs
StatePublished - Nov 1993

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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