Investigating Gene-Environment Interactions in Multiple Cohorts of 1990-1991 Gulf War Veterans
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1071678
Entities
People
- Patricia J. Lloyd
Organizations
- Boston University School of Public Health