A Psychobiological Approach to Gulf War Illness: Acute Exercise & DNA Methylation
Alexander E. Boruch
Thesis advisor: Dane B. Cook
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Background
Gulf War Illness (GWI) is a form of chronic multi-symptom illness characterized by medically unexplained and heterogenous symptoms (e.g., fatigue, pain, cognitive decline) that affect ~30% of personnel deployed during the 1990-1991 Persian Gulf War.
Controlled high- intensity or maximal aerobic exercise (i.e., an exercise challenge) have been used to modulate physiological stress responses in GWI. Investigations of DNA methylation in GWI are seldom, and exercise-induced changes in DNA methylation may provide insight into the molecular interactions underlying GWI pathophysiology.
Purpose
The primary purpose of the present dissertation is to compare differences in DNA methylation following an acute aerobic exercise challenge in Gulf War Veterans with and without GWI.
Methods
Differences in DNA methylation measured via microarray were tested in Gulf War Veterans with GWI (N = 27) compared to control Gulf War Veterans (N = 25) pre-, 30-minutes post-, and 24 hours post-exercise. Associations between DNA methylation, ventilatory equivalents during exercise, and pre-post symptom responses were also tested in Gulf War Veterans with and without GWI.
Results
Gulf War Veterans with GWI had differentially methylated positions (DMPs) in genes with established metabolic and immune functions, and DMP-associated genes with select inflammatory functions (e.g., response to IFN-β) were observed only after exercise.
Select DMPs were significantly associated with fatigue and mood disturbance 30-minutes post-exercise, and pre-exercise a DMP within the oxoglutarate dehydrogenase [OGDH] demonstrated modest classification accuracy (Area Under the Curve [AUC] = 0.796) between GWI cases compared to controls.
Conclusions
DMP-associated genes that participate in inflammation and metabolism are consistent with previous GWI investigations, including those that have studied DNA methylation. DNA methylation changes following an exercise challenge support involvement from the immune and metabolic systems in GWI pathophysiology and signify potential heightened risk of chronic comorbidities (e.g., cardiovascular or metabolic disease)
Web | PDF | Thesis: University of Wisconsin-Madison | Open Access
Alexander E. Boruch
Thesis advisor: Dane B. Cook
[Line breaks added]
Background
Gulf War Illness (GWI) is a form of chronic multi-symptom illness characterized by medically unexplained and heterogenous symptoms (e.g., fatigue, pain, cognitive decline) that affect ~30% of personnel deployed during the 1990-1991 Persian Gulf War.
Controlled high- intensity or maximal aerobic exercise (i.e., an exercise challenge) have been used to modulate physiological stress responses in GWI. Investigations of DNA methylation in GWI are seldom, and exercise-induced changes in DNA methylation may provide insight into the molecular interactions underlying GWI pathophysiology.
Purpose
The primary purpose of the present dissertation is to compare differences in DNA methylation following an acute aerobic exercise challenge in Gulf War Veterans with and without GWI.
Methods
Differences in DNA methylation measured via microarray were tested in Gulf War Veterans with GWI (N = 27) compared to control Gulf War Veterans (N = 25) pre-, 30-minutes post-, and 24 hours post-exercise. Associations between DNA methylation, ventilatory equivalents during exercise, and pre-post symptom responses were also tested in Gulf War Veterans with and without GWI.
Results
Gulf War Veterans with GWI had differentially methylated positions (DMPs) in genes with established metabolic and immune functions, and DMP-associated genes with select inflammatory functions (e.g., response to IFN-β) were observed only after exercise.
Select DMPs were significantly associated with fatigue and mood disturbance 30-minutes post-exercise, and pre-exercise a DMP within the oxoglutarate dehydrogenase [OGDH] demonstrated modest classification accuracy (Area Under the Curve [AUC] = 0.796) between GWI cases compared to controls.
Conclusions
DMP-associated genes that participate in inflammation and metabolism are consistent with previous GWI investigations, including those that have studied DNA methylation. DNA methylation changes following an exercise challenge support involvement from the immune and metabolic systems in GWI pathophysiology and signify potential heightened risk of chronic comorbidities (e.g., cardiovascular or metabolic disease)
Web | PDF | Thesis: University of Wisconsin-Madison | Open Access