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


CONCLUSIONS
These data demonstrate an association between PAF-AH allelic variation, plasma activity, and outcome in ARDS.
Li
S
S
Clinical Pharmacology, Quintiles, Inc., Overland Park, KS, USA.
Stuart
L
L
Zhang
Y
Y
Meduri
G U
GU
Umberger
R
R
Yates
C R
CR
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012128:Respiratory Distress Syndrome / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D017741:Survivors
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase