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

Robert W. Haley, Scott Billecke, Bert N. La Du

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

Abstract

Previously Haley et al. described six possible syndromes identified by factor analysis of symptoms in Gulf War veterans and demonstrated that veterans with these symptom complexes were more neurologically impaired than age-sex-education-matched well controls. They also uncovered strong associations (relative risks 4-8) suggesting that these symptom complexes were related to wartime exposure to combinations of organophosphate pesticides, chemical nerve agents, high concentration DEET insect repellant, and symptoms of advanced acute toxicity after taking pyridostigmine. Here we have shown that compared to controls, ill veterans with the neurologic symptom complexes were more likely to have the R allele (heterozygous QR or homozygous R) than to be homozygous Q for the paraoxonase/arylesterase 1 (PON1) gene. Moreover, low activity of the PON1 type Q (Gln192, formerly designated type A) arylesterase allozyme distinguished ill veterans from controls better than just the PON1 genotype or the activity levels of the type R (Arg192, formerly designated type B) arylesterase allozyme, total arylesterase, total paraoxonase, or butyrylcholinesterase. A history of advanced acute toxicity after taking pyridostigmine was also correlated with low PON1 type Q arylesterase activity. Type Q is the allozyme of paraoxonase/arylesterase that most efficiently hydrolyzes several organophosphates including sarin, soman, and diazinon. These findings further support the proposal that neurologic symptoms in some Gulf War veterans were caused by environmental chemical exposures.

Original languageEnglish (US)
Pages (from-to)227-233
Number of pages7
JournalToxicology and Applied Pharmacology
Volume157
Issue number3
DOIs
StatePublished - Jun 15 1999

Keywords

  • Brain, drug effects
  • Butyrylcholinesterase
  • Chemical warfare agents
  • Epidemiology
  • Esterases, blood
  • Heterozygote
  • Homozygote
  • Human
  • Isoenzymes
  • Military personnel
  • Organophosphorus compounds
  • Paraoxonase
  • Persian Gulf syndrome
  • Polymorphism (genetics)
  • Pyridostigmine bromide
  • Risk factors
  • Support, U.S. gov't, D.O.D.
  • Support, non-U.S. gov't
  • Veterans

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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