Veterans with Gulf War Illness (GWI) — a chronic multi-symptom disorder not currently diagnosed by standard medical or laboratory tests — have mitochondrial DNA (mtDNA) damage consistent with mitochondrial dysfunction, a new study shows.
The study, “Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness,” appeared in the journal PLOS ONE.
About 30 percent of U.S. troops who served during the 1990-91 Gulf War have GWI, whose symptoms include fatigue, widespread pain, exercise intolerance and cognitive dysfunction. Since the symptoms of GWI tend to be related to energy metabolism, mitochondrial dysfunction may play a role.
In fact, military deployment often involves exposure to environmental toxins such as carbamates and organophosphates that have been shown to cause mitochondrial dysfunction. Oxidative stress can lead to mitochondrial DNA mutations and damage mitochondrial proteins. Yet until now, no studies have assessed the linkage between mitochondrial DNA damage and GWI.
This led researchers at the Department of Veterans Affairs New Jersey Health Care System in East Orange, N.J., to conduct a study to determine if GWI patients have elevated markers of mitochondrial damage and function compared to the general population. They used a technique called QPCR (Quantitative Polymerase Chain Reaction) to measure the expression of known genes related to mitochondrial and nuclear DNA damage.
Researchers recruited 21 GWI patients and seven controls. They collected blood samples and conducted QPCR tests on all 28 to measure mitochondrial and nuclear DNA mutation frequency. In addition, researchers measured mitochondrial DNA copy number alterations and nuclear DNA lesion frequency in order to determine gene expression of important mitochondrial complexes (I and IV) – both of which are involved in energy metabolism. Enzyme activity for those proteins was also measured.
Results showed that veterans with GWI had a higher frequency of mtDNA mutations and higher mtDNA copy numbers than did controls. They also had more frequent nuclear DNA lesions, but the difference was not statistically significant.
Activity of complexes I and IV were similar between the groups, though high mtDNA lesion frequency was correlated with lower complex I and IV enzyme activity. Therefore, veterans with GWI tend to have greater mtDNA damage.
“Future studies are necessary to confirm our findings. However, this work suggests that mtDNA damage may serve as an objective biomarker of GWI,” authors concluded. “Results from the present study, along with recent work from other laboratories, suggest mitochondrial dysfunction is involved in the pathobiology [disease development] of GWI and should continue to be actively investigated.”