Investigating Gene-Environment Interactions in Multiple Cohorts of 1990-1991 Gulf War Veterans
Technical Report,30 Sep 2017,29 Sep 2018
Boston University School of Public Health Boston United States
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While the 1990-91 Gulf War was relatively short, military personnel who served in the war have suffered long-lasting health consequences. The constellation of health symptoms known as Gulf War Illness GWI affects up to one third of 1991 Gulf War veterans. Epidemiologic studies have consistently identified neurotoxicant exposures as the most prominent risk factors for GWI, but an important question remains concerning why some veterans became ill after the war, while others with similar exposures did not. The most prominent exposures of concern include 1 prolonged use of pyridostigmine bromide PB pills, a carbamate compound, 2 excessive use of pesticides including organophosphates OPs and carbamates and 3 chemical nerve agents OPs. These compounds have a shared mechanism of action in that they inhibit acetylcholinesterase AChE and alter levels of the neurotransmitter acetylcholine, with potential acute and long-term effects on the brain and nervous system. Genetic variability in veterans ability to neutralize these compounds has long been hypothesized to explain why some veterans got sick and others remained healthy. The human body produces enzymes that protect against adverse effects of cholinergic toxicants, including the enzyme butyrylcholinesterase BChE. Recent findingsfrom Steele et al 2015 provided preliminary evidence that veterans with slow-acting BChE genetic variants may have been at dramatically increased risk for GWI OR 40.0, p 0.0005 if they used PB during deployment. An additional enzyme, paraoxonase-1 PON1, catalyzes the hydrolysis of OPs and has also been suggested as a factor that contributed to differences in vulnerability to Gulf War neurotoxicants in theater.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology