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-Reference-Cited by-同舟云学术

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

Published:2024-07-24 Issue:8 Volume:21 Page:964
ISSN:1660-4601
Container-title:International Journal of Environmental Research and Public Health
language:en
Short-container-title:IJERPH

Author:

Steele Lea¹,Furlong Clement E.²³,Richter Rebecca J.²^ORCID,Marsillach Judit⁴^ORCID,Janulewicz Patricia A.⁵,Krengel Maxine H.⁶,Klimas Nancy G.⁷⁸^ORCID,Sullivan Kimberly⁵^ORCID,Chao Linda L.⁹¹⁰¹¹^ORCID

Affiliation:

1. Veterans Health Research Program, Yudofsky Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA

2. Department of Medicine (Division Medical Genetics), University of Washington, Seattle, WA 98195, USA

3. Department of Genome Sciences, University of Washington, Seattle, WA 98105, USA

4. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA

5. Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USA

6. Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA

7. Dr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuroimmune Medicine, Nova Southeastern University, Fort Lauderdale, FL 22238, USA

8. Geriatric Research Education and Clinical Center, Miami Veterans Affaris Medical Center, Miami, FL 22125, USA

9. Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94142, USA

10. Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA 94142, USA

11. San Francisco Veterans Affairs Health Care System, 4150 Clement Street (114M), San Francisco, CA 94121, USA

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 PON1192 variants with different capacities for neutralizing specific chemicals, including certain acetylcholinesterase inhibitors. Methods: We evaluated PON1192 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 PON1192 subgroups. Exact logistic regression explored effects of exposure combinations in PON1192 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 PON1192 exposures and exposure–exposure interactions in the development of GWI.

Funder

the U.S. Department of Defense Congressionally Directed Medical Research Program (CDMRP) Gulf War Illness Research Program

Publisher

MDPI AG

Link

https://www.mdpi.com/1660-4601/21/8/964/pdf

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