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

S Li, L Stuart, Y Zhang, G U Meduri, R Umberger, C R Yates

Clinical Pharmacology, Quintiles, Inc., Overland Park, KS, USA.

Journal of clinical pharmacy and therapeutics 2009 Aug

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

Citation

S Li, L Stuart, Y Zhang, G U Meduri, R Umberger, C R Yates. Inter-individual variability of plasma PAF-acetylhydrolase activity in ARDS patients and PAFAH genotype. Journal of clinical pharmacy and therapeutics. 2009 Aug;34(4):447-55