SOD2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in Gulf war veterans

Abstract Multiple chemical sensitivity (MCS), though viewed by many as psychogenic, was presumptively tied to genetic variation in superoxide dismutase 2 (SOD2), involved in conversion of mitochondrial superoxide to hydrogen peroxide, in Japanese paper pulp workers. Gulf War veterans (GWV) have incr...

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Main Authors: Beatrice Alexandra Golomb, Leeann Bui, Brinton Keith Berg
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-09916-w
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author Beatrice Alexandra Golomb
Leeann Bui
Brinton Keith Berg
author_facet Beatrice Alexandra Golomb
Leeann Bui
Brinton Keith Berg
author_sort Beatrice Alexandra Golomb
collection DOAJ
description Abstract Multiple chemical sensitivity (MCS), though viewed by many as psychogenic, was presumptively tied to genetic variation in superoxide dismutase 2 (SOD2), involved in conversion of mitochondrial superoxide to hydrogen peroxide, in Japanese paper pulp workers. Gulf War veterans (GWV) have increased MCS compared to nondeployed persons. In data from GWV and nonveterans, we assessed whether altered oxidative stress management via SOD2 polymorphism was tied to self-rated chemical sensitivity. Sixty white predominantly male GWV and age-similar nonveterans completed self-ratings of chemical sensitivity, and underwent both nuclear DNA analysis for SOD2 variants and mitochondrial haplogroup assessment. SOD2 Ala16 (vs. Val16) significantly predicted self-rated chemical sensitivity in GWV and in the total sample (ordinal logistic regression with robust SEs): OR(SE)[95% CI] = 3.56(1.83)[1.30, 9.74], p = 0.013 (total sample); OR[95% CI](SE) = 6.36(4.85)[1.42, 28.4], p = 0.015 (Gulf-deployed). Significance was sustained with adjustment for mitochondrial haplogroup U (not itself significant) and when reappraised with nonparametric trend tests (Kendall’s Tau, Spearman Ranked Correlation Coefficient). The findings extend evidence of SOD2 polymorphism ramifications for chemical sensitivity to a new chemically exposed sample, implicating mitochondrial oxidative stress management as a (though not necessarily the exclusive) key factor in chemical sensitivity. Findings comport with burgeoning evidence inculpating mitochondrial impairment and oxidative stress in many drug/chemical/environmental factors’ toxicity irrespective of the agent’s nominal mechanism of action. This supports chemical sensitivity as a physiological, not a psychogenic condition.
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spelling doaj-art-4d108fb069cd49c7a91608390d3f1cdb2025-08-20T03:42:49ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-09916-wSOD2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in Gulf war veteransBeatrice Alexandra Golomb0Leeann Bui1Brinton Keith Berg2Department of Medicine, UC San Diego School of MedicineDepartment of Medicine, UC San Diego School of MedicineDepartment of Medicine, UC San Diego School of MedicineAbstract Multiple chemical sensitivity (MCS), though viewed by many as psychogenic, was presumptively tied to genetic variation in superoxide dismutase 2 (SOD2), involved in conversion of mitochondrial superoxide to hydrogen peroxide, in Japanese paper pulp workers. Gulf War veterans (GWV) have increased MCS compared to nondeployed persons. In data from GWV and nonveterans, we assessed whether altered oxidative stress management via SOD2 polymorphism was tied to self-rated chemical sensitivity. Sixty white predominantly male GWV and age-similar nonveterans completed self-ratings of chemical sensitivity, and underwent both nuclear DNA analysis for SOD2 variants and mitochondrial haplogroup assessment. SOD2 Ala16 (vs. Val16) significantly predicted self-rated chemical sensitivity in GWV and in the total sample (ordinal logistic regression with robust SEs): OR(SE)[95% CI] = 3.56(1.83)[1.30, 9.74], p = 0.013 (total sample); OR[95% CI](SE) = 6.36(4.85)[1.42, 28.4], p = 0.015 (Gulf-deployed). Significance was sustained with adjustment for mitochondrial haplogroup U (not itself significant) and when reappraised with nonparametric trend tests (Kendall’s Tau, Spearman Ranked Correlation Coefficient). The findings extend evidence of SOD2 polymorphism ramifications for chemical sensitivity to a new chemically exposed sample, implicating mitochondrial oxidative stress management as a (though not necessarily the exclusive) key factor in chemical sensitivity. Findings comport with burgeoning evidence inculpating mitochondrial impairment and oxidative stress in many drug/chemical/environmental factors’ toxicity irrespective of the agent’s nominal mechanism of action. This supports chemical sensitivity as a physiological, not a psychogenic condition.https://doi.org/10.1038/s41598-025-09916-w
spellingShingle Beatrice Alexandra Golomb
Leeann Bui
Brinton Keith Berg
SOD2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in Gulf war veterans
Scientific Reports
title SOD2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in Gulf war veterans
title_full SOD2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in Gulf war veterans
title_fullStr SOD2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in Gulf war veterans
title_full_unstemmed SOD2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in Gulf war veterans
title_short SOD2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in Gulf war veterans
title_sort sod2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in gulf war veterans
url https://doi.org/10.1038/s41598-025-09916-w
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