Determinants of plasma platelet-activating factor acetylhydrolase: Heritability and relationship to plasma lipoproteins

Rudy Guerra, Biren Zhao, Vincent Mooser, Diana Stafforini, John M. Johnston, Jonathan C. Cohen

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Plasma platelet-activating factor acetylhydrolase (PAF-AH) is the enzyme that inactivates PAF (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine). We determined the relative contributions of genetic and environmental factors to variation in plasma PAF-AH activity in 240 individuals from 60 nuclear families. Regression of mean-offspring PAF-AH activity on the mid-parent value indicated that 62% of the variation in plasma PAF-AH activity was heritable. Spousal values were weakly negatively correlated, indicating that familial aggregation of PAF-AH activity is due to genetic rather than to environmental factors. Among normolipidemic individuals, plasma PAF-AH activity was strongly correlated with the plasma concentration of low density lipoprotein cholesterol (LDL-C), and treatment with lovastatin resulted in proportional decreases in plasma PAF-AH activity and LDL-C concentrations. To further elucidate the relationship between PAF-AH and plasma concentrations of LDL, plasma PAF-AH activity was measured in families with well-defined, monogenic disorders of LDL metabolism. Plasma PAF-AH activity cosegregated with plasma LDL-C concentrations in familial hypercholesterolemia, but not in familial hypobetalipoproteinemia. We speculate that the rate of removal of LDL from the circulation may determine the clearance rate of PAF-AH, hereby modulating the activity of PAF-AH in blood.

Original languageEnglish (US)
Pages (from-to)2281-2288
Number of pages8
JournalJournal of lipid research
Volume38
Issue number11
StatePublished - Nov 1 1997

Keywords

  • Familial hypercholesterolemia
  • Familial hypobetalipoproteinemia
  • Lovastatin
  • Low density lipoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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