Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans

Previously Haley et al. described six possible syndromes identified by fact or analysis of symptoms in Gulf War veterans and demonstrated that veterans with these symptom complexes were more neurologically impaired than age-se x-education-matched well controls. They also uncovered strong associations (relative risks 4-8) suggesting that these symptom complexes were related t o wartime exposure to combinations of organophosphate pesticides, chemical nerve agents, high concentration DEET insect repellant, and symptoms of adv anced acute toxicity after taking pyridostigmine. Here we have shown that c ompared to controls, ill veterans with the neurologic symptom complexes wer e more likely to have the R allele (heterozygous QR or homozygous R) than t o be homozygous Q for the paraoxonase/arylesterase 1 (PON1) gene. Moreover, low activity of the PON1 type Q (Gln(192), formerly designated type A) ary lesterase allozyme distinguished ill veterans from controls better than jus t the PON1 genotype or the activity levels of the type R (Arg(192), formerl y designated type B) arylesterase allozyme, total arylesterase, total parao xonase, or butyrylcholinesterase. A history of advanced acute toxicity afte r taking pyridostigmine was also correlated with low PON1 type Q arylestera se activity. Type Q is the allozyme of paraoxonase/arylesterase that most e fficiently hydrolyzes several organophosphates including sarin, soman, and diazinon. These findings further support the proposal that neurologic sympt oms in some Gulf War veterans were caused by environmental chemical exposur es. (C) 1999 Academic Press.