Abstract
About 25–35% of United States veterans who fought in the 1990–1991 Gulf War report several moderate or severe chronic systemic symptoms, defined as Gulf War illness (GWI). Thirty years later, there is little consensus on the causes or biological underpinnings of GWI. The Gulf War Era Cohort and Biorepository (GWECB) was designed to investigate genetic and environmental associations with GWI and consists of 1343 veterans. We investigate candidate gene–toxicant interactions that may be associated with GWI based on prior associations found in human and animal model studies, focusing on SNPs in or near ACHE, BCHE, and PON1 genes to replicate results from prior studies. SOD1 was also considered as a candidate gene. CDC Severe GWI, the primary outcome, was observed in 26% of the 810 deployed veterans included in this study. The interaction between the candidate SNP rs662 and pyridostigmine bromide (PB) pills was found to be associated with CDC Severe GWI. Interactions between PB pill exposure and rs3917545, rs3917550, and rs2299255, all in high linkage disequilibrium in PON1, were also associated with respiratory symptoms. These SNPs could point toward biological pathways through which GWI may develop, which could lead to biomarkers to detect GWI or to better treatment options for veterans with GWI.
Highlights
Gulf War veterans began reporting chronic systemic symptoms almost immediately after returning from deployment to the Gulf in support of the 1990–1991 Gulf War [1,2,3,4]
Inhibition of acetylcholinesterase function is often cited as an explanation for why the pesticides, pyridostigmine bromide (PB), and nerve agents are suspected to be in the causal pathway of Gulf War illness (GWI) [7,12,15,16,17,18,19,20,21,22]
Veterans who fulfill the CDC Severe GWI criteria and those who do not are distributed by sex, age group, and OEF/OIF deployment
Summary
Gulf War veterans began reporting chronic systemic symptoms almost immediately after returning from deployment to the Gulf in support of the 1990–1991 Gulf War [1,2,3,4]. Summarizing several decades of research on GW exposures, the VA Gulf War Research Advisory Council identified pyridostigmine bromide (PB) pills and the use of pesticides as being consistently associated with chronic multisymptom illness in multivariable adjusted models [12]. These consistently observed associations with PB and pesticide exposures suggest biological pathways, enzymes and genes for consideration in genetic analysis. Rodent models for GWI have been developed using combinations of pesticides, PB, sarin surrogate diisopropyl fluorophosphate (DFP), and chronic stress or corticosterone [15,16,17,19,23,24,25,26,27,28,29]
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