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

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. © 2009 Blackwell Publishing Ltd.

Publication Title

Journal of Clinical Pharmacy and Therapeutics

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