# Genetics of epigenetic response to high circulating glucocorticoids and organophosphorus compounds

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2024 · $580,839

## Abstract

The USA sent approximately 700,000 troops to the Persian Gulf to participate in the
1990-91 Gulf War. Of those who returned, 25-30% complained of a generalized
malaise with gastrointestinal, endocrinological, respiratory and neurological
complaints, which was named Gulf War Illness (GWI). Many of those returning with
GWI are still sick nearly 30 years after their exposure, with no cure. What changes
allow these symptoms to persist over many years? Genetic variation among the
troops may have caused them to respond differently to the exposure. Epigenetic
alterations in gene regulation are the most likely candidate for the persistence of
symptoms. We and others have developed an exposure regime in mice that mimics
both troop exposures and biological effects of GWI. This model uses corticosterone
pretreatment (CORT; to simulate physiological stress) combined with an irreversible
acetylcholinesterase inhibitor, diisopropyl fluorophosphate (DFP); as troops were
exposed to many acetylcholinesterase inhibitors. Initial studies showed acute
changes in proinflammatory cytokine genes and changes in methylation of genes
following exposure to CORT combined with DFP. PI Jones and colleagues have
seen significant differences in proinflammatory gene expression response to the
treatment among more than 25 different genotypes (i.e., inbred mouse strains) and
have been able to map quantitative trait loci which mediate this effect. The proposed
research takes the next step to understand the genetics of epigenetic changes
related to the persistence of GWI.

## Key facts

- **NIH application ID:** 10769749
- **Project number:** 5R01ES031656-04
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Byron C Jones
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $580,839
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769749

## Citation

> US National Institutes of Health, RePORTER application 10769749, Genetics of epigenetic response to high circulating glucocorticoids and organophosphorus compounds (5R01ES031656-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10769749. Licensed CC0.

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