PON1 Status in Relation to Gulf War Illness: Evidence of Gene–Exposure Interactions from a Multisite Case–Control Study of 1990–1991 Gulf War Veterans

Lea Steele, Clement E. Furlong, Rebecca J. Richter, Judit Marsillach, Patricia A. Janulewicz, Maxine H. Krengel, Nancy G. Klimas, Kimberly Sullivan and Linda L. Chao ()
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Lea Steele: Veterans Health Research Program, Yudofsky Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA
Clement E. Furlong: Department of Medicine (Division Medical Genetics), University of Washington, Seattle, WA 98195, USA
Rebecca J. Richter: Department of Medicine (Division Medical Genetics), University of Washington, Seattle, WA 98195, USA
Judit Marsillach: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
Patricia A. Janulewicz: Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USA
Maxine H. Krengel: Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA
Nancy G. Klimas: Dr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuroimmune Medicine, Nova Southeastern University, Fort Lauderdale, FL 22238, USA
Kimberly Sullivan: Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USA
Linda L. Chao: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94142, USA

IJERPH, 2024, vol. 21, issue 8, 1-19

Abstract: Background: Deployment-related neurotoxicant exposures are implicated in the etiology of Gulf War illness (GWI), the multisymptom condition associated with military service in the 1990–1991 Gulf War (GW). A Q/R polymorphism at position 192 of the paraoxonase (PON)-1 enzyme produce PON1 192 variants with different capacities for neutralizing specific chemicals, including certain acetylcholinesterase inhibitors. Methods: We evaluated PON1 192 status and GW exposures in 295 GWI cases and 103 GW veteran controls. Multivariable logistic regression determined independent associations of GWI with GW exposures overall and in PON1 192 subgroups. Exact logistic regression explored effects of exposure combinations in PON1 192 subgroups. Results: Hearing chemical alarms (proxy for possible nerve agent exposure) was associated with GWI only among RR status veterans (OR = 8.60, p = 0.014). Deployment-related skin pesticide use was associated with GWI only among QQ (OR = 3.30, p = 0.010) and QR (OR = 4.22, p < 0.001) status veterans. Exploratory assessments indicated that chemical alarms were associated with GWI in the subgroup of RR status veterans who took pyridostigmine bromide (PB) (exact OR = 19.02, p = 0.009) but not RR veterans who did not take PB (exact OR = 0.97, p = 1.00). Similarly, skin pesticide use was associated with GWI among QQ status veterans who took PB (exact OR = 6.34, p = 0.001) but not QQ veterans who did not take PB (exact OR = 0.59, p = 0.782). Conclusion: Study results suggest a complex pattern of PON1 192 exposures and exposure–exposure interactions in the development of GWI.

Keywords: PON1; Gulf War illness; Gulf War veterans; deployment-related exposures; organophosphate; pesticides; pyridostigmine bromide; gene–environment interaction (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2024
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