Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0711986105
Acetylcholinesterase inhibitors and Gulf War illnesses
http://www.pnas.org/cgi/content/abstract/0711986105v1
Department of Medicine, University of California, San Diego, CA 92093-0995
Communicated by Stephen F. Heinemann, Salk Institute for Biological Studies, San Diego, CA, January 15, 2008 (received for review December 5, 2006)
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
Author contributions: B.A.G. designed research, performed research, analyzed data, and wrote the paper.
The author declares no conflict of interest.
*E-mail: bgolomb@ucsd.edu
© 2008 by The National Academy of Sciences of the USA
