Abstract
BackgroundEpidemiologic studies have implicated wartime exposures to acetylcholinesterase (AChE)-inhibiting chemicals as etiologic factors in Gulf War illness (GWI), the multisymptom condition linked to military service in the 1991 Gulf War. It is unclear, however, why some veterans developed GWI while others with similar exposures did not. Genetic variants of the enzyme butyrylcholinesterase (BChE) differ in their capacity for metabolizing AChE-inhibiting chemicals, and may confer differences in biological responses to these compounds. The current study assessed BChE enzyme activity and BChE genotype in 1991 Gulf War veterans to evaluate possible association of this enzyme with GWI.MethodsThis case–control study evaluated a population-based sample of 304 Gulf War veterans (144 GWI cases, meeting Kansas GWI criteria, and 160 controls). BChE enzyme activity levels and genotype were compared, overall, in GWI cases and controls. Potential differences in risk associated with cholinergic-related exposures in theater were explored using stratified analyses to compare associations between GWI and exposures in BChE genetic and enzyme activity subgroups.ResultsOverall, GWI cases and controls did not differ by mean BChE enzyme activity level or by BChE genotype. However, for the subgroup of Gulf War veterans with less common, generally less active, BChE genotypes (K/K, U/AK, U/A, A/F, AK/F), the association of wartime use of pyridostigmine bromide (PB) with GWI (OR = 40.00, p = 0.0005) was significantly greater than for veterans with the more common U/U and U/K genotypes (OR = 2.68, p = 0.0001).ConclusionsStudy results provide preliminary evidence that military personnel with certain BChE genotypes who used PB during the 1991 Gulf War may have been at particularly high risk for developing GWI. Genetic differences in response to wartime exposures are potentially important factors in GWI etiology and should be further evaluated in conjunction with exposure effects.
Highlights
Epidemiologic studies have implicated wartime exposures to acetylcholinesterase (AChE)-inhibiting chemicals as etiologic factors in Gulf War illness (GWI), the multisymptom condition linked to military service in the 1991 Gulf War
Epidemiologic studies of Gulf War veterans consistently indicate that GWI is not associated with combat stressors, when effects of other wartime exposures are taken into account, and that rates of psychiatric illness associated with the brief 1991 conflict are substantially lower than for other wars [2,20,21]
Veterans are excluded as GWI cases if they report being diagnosed with any from a list of chronic medical conditions that might account for their symptoms, or severe psychiatric conditions that might preclude their ability to accurately report symptoms
Summary
Epidemiologic studies have implicated wartime exposures to acetylcholinesterase (AChE)-inhibiting chemicals as etiologic factors in Gulf War illness (GWI), the multisymptom condition linked to military service in the 1991 Gulf War. Studies of veteran populations in the U.S and other countries have consistently described a profile of chronic symptoms that afflict veterans of the 1991 Gulf War at significantly excess rates, compared to other veteran groups. This condition, commonly known as Gulf War illness (GWI), is estimated to affect between one fourth and one third of the nearly 700,000 U.S veterans who served in the 1991 conflict [1,2,3,4]. Epidemiologic studies of Gulf War veterans consistently indicate that GWI is not associated with combat stressors, when effects of other wartime exposures are taken into account, and that rates of psychiatric illness associated with the brief 1991 conflict are substantially lower than for other wars [2,20,21]
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