Inter-individual variability of plasma PAF-acetylhydrolase activity in ARDS patients and PAFAH genotype

J Clin Pharm Ther. 2009 Aug;34(4):447-55. doi: 10.1111/j.1365-2710.2008.01014.x.

Abstract

Background: Platelet activating factor (PAF), a pro-inflammatory phospholipid, stimulates cytokine secretion from polymorphonuclear leukocytes expressing the transmembrane G-protein coupled PAF receptor. Elevated PAF levels are associated with acute respiratory distress syndrome (ARDS) and sepsis severity. The pro-inflammatory effects of PAF are terminated by PAF acetylhydrolase (PAF-AH).

Objective: We sought to determine whether allelic variants in the human PAFAH gene (Arg92His, Ile198Thr, and Ala379Val) contribute to variability in PAF-AH activity in patient plasma obtained within 72 h of ARDS diagnosis.

Results: Plasma PAF-AH activity (mean +/- SD) was higher in patients homozygous for the Arg92 allele compared to His92 allele carriers (2.21 +/- 0.77 vs. 1.64 +/- 0.68 U/min; P < 0.01; n = 31 and 21 respectively). Baseline plasma PAF-AH activity was higher among day 7 survivors vs. day 7 non-survivors (2.05 +/- 0.75 vs. 1.27 +/- 0.63, P = 0.05).

Conclusion: These data demonstrate an association between PAF-AH allelic variation, plasma activity, and outcome in ARDS.

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / metabolism*
  • Adult
  • Aged
  • Alleles
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Respiratory Distress Syndrome / diagnosis
  • Respiratory Distress Syndrome / enzymology
  • Respiratory Distress Syndrome / genetics*
  • Survivors

Substances

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase