TY - JOUR
T1 - Gene–Toxicant Interactions in Gulf War Illness
T2 - Differential Effects of the PON1 Genotype
AU - Vahey, Jacqueline
AU - Gifford, Elizabeth J.
AU - Sims, Kellie J.
AU - Chesnut, Blair
AU - Boyle, Stephen H.
AU - Stafford, Crystal
AU - Upchurch, Julie
AU - Stone, Annjanette
AU - Pyarajan, Saiju
AU - Efird, Jimmy T.
AU - Williams, Christina D.
AU - Hauser, Elizabeth R.
N1 - Funding Information:
Funding: This research was funded by the Department of Veteran Affairs, Cooperative Studies Program CSP585. J.V. received support from the Duke University Department of Biostatistics and Bioinformatics and through the T32 training grant (5T32-GM071340).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - GWI
KW - Gene– environment interactions
KW - Gulf War illness
KW - PON1
KW - Pesticides
KW - Pyridostigmine bromide
KW - Veteran health
UR - http://www.scopus.com/inward/record.url?scp=85122753594&partnerID=8YFLogxK
U2 - 10.3390/BRAINSCI11121558
DO - 10.3390/BRAINSCI11121558
M3 - Article
AN - SCOPUS:85122753594
SN - 2076-3425
VL - 11
JO - Brain Sciences
JF - Brain Sciences
IS - 12
M1 - 1558
ER -