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Research Article

Acetylcholinesterase inhibitors and Gulf War illnesses

Beatrice Alexandra Golomb
  1. Department of Medicine, University of California, San Diego, CA 92093-0995

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PNAS March 18, 2008 105 (11) 4295-4300; https://doi.org/10.1073/pnas.0711986105
Beatrice Alexandra Golomb
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  • For correspondence: bgolomb@ucsd.edu
  1. Communicated by Stephen F. Heinemann, Salk Institute for Biological Studies, San Diego, CA, January 15, 2008 (received for review December 5, 2006)

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Abstract

Increasing evidence suggests excess illness in Persian Gulf War veterans (GWV) can be explained in part by exposure of GWV to organophosphate and carbamate acetylcholinesterase inhibitors (AChEis), including pyridostigmine bromide (PB), pesticides, and nerve agents. Evidence germane to the relation of AChEis to illness in GWV was assessed. Many epidemiological studies reported a link between AChEi exposure and chronic symptoms in GWV. The link is buttressed by a dose–response relation of PB pill number to chronic symptoms in GWV and by a relation between avidity of AChEi clearance and illness, based on genotypes, concentrations, and activity levels of enzymes that detoxify AChEis. Triangulating evidence derives from studies linking occupational exposure to AChEis to chronic health symptoms that mirror those of ill GWV. Illness is again linked to lower activity of AChEi detoxifying enzymes and genotypes conferring less-avid AChEi detoxification. AChEi exposure satisfies Hill's presumptive criteria for causality, suggesting this exposure may be causally linked to excess health problems in GWV.

  • Gulf War veteran
  • pyridostigmine
  • pesticide
  • sarin
  • organophosphate

Footnotes

  • E-mail: bgolomb{at}ucsd.edu
  • Author contributions: B.A.G. designed research, performed research, analyzed data, and wrote the paper.

  • The author declares no conflict of interest.

  • This article contains supporting information online at www.pnas.org/cgi/content/full/0711986105/DC1.

  • © 2008 by The National Academy of Sciences of the USA
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Acetylcholinesterase inhibitors and Gulf War illnesses
Beatrice Alexandra Golomb
Proceedings of the National Academy of Sciences Mar 2008, 105 (11) 4295-4300; DOI: 10.1073/pnas.0711986105

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Acetylcholinesterase inhibitors and Gulf War illnesses
Beatrice Alexandra Golomb
Proceedings of the National Academy of Sciences Mar 2008, 105 (11) 4295-4300; DOI: 10.1073/pnas.0711986105
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