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PLoS One. 2017 Sep 14;12(9):e0184832. doi: 10.1371/journal.pone.0184832. eCollection 2017.

Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness.

Author information

1
War Related Illness and Injury Study Center, Veterans Affairs New Jersey Health Care System, East Orange, New Jersey, United States of America.
2
New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, United States of America.
3
Nicholas School of the Environment, Duke University, Durham, North Carolina, United States of America.
4
Pain and Fatigue Study Center, Beth Israel Medical Center and Albert Einstein Medical Center, New York, New York, United States of America.
5
Surgical Services, Veterans Affairs New Jersey Health Care System, East Orange, New Jersey, United States of America.

Abstract

Gulf War Illness (GWI) is a chronic multi-symptom illness not currently diagnosed by standard medical or laboratory test that affects 30% of veterans who served during the 1990-1991 Gulf War. The clinical presentation of GWI is comparable to that of patients with certain mitochondrial disorders-i.e., clinically heterogeneous multisystem symptoms. Therefore, we hypothesized that mitochondrial dysfunction may contribute to both the symptoms of GWI as well as its persistence over time. We recruited 21 cases of GWI (CDC and Kansas criteria) and 7 controls to participate in this study. Peripheral blood samples were obtained in all participants and a quantitative polymerase chain reaction (QPCR) based assay was performed to quantify mitochondrial and nuclear DNA lesion frequency and mitochondrial DNA (mtDNA) copy number (mtDNAcn) from peripheral blood mononuclear cells. Samples were also used to analyze nuclear DNA lesion frequency and enzyme activity for mitochondrial complexes I and IV. Both mtDNA lesion frequency (p = 0.015, d = 1.13) and mtDNAcn (p = 0.001; d = 1.69) were elevated in veterans with GWI relative to controls. Nuclear DNA lesion frequency was also elevated in veterans with GWI (p = 0.344; d = 1.41), but did not reach statistical significance. Complex I and IV activity (p > 0.05) were similar between groups and greater mtDNA lesion frequency was associated with reduced complex I (r2 = -0.35, p = 0.007) and IV (r2 = -0.28, p < 0.01) enzyme activity. In conclusion, veterans with GWI exhibit greater mtDNA damage which is consistent with mitochondrial dysfunction.

PMID:
28910366
PMCID:
PMC5599026
DOI:
10.1371/journal.pone.0184832
[Indexed for MEDLINE]
Free PMC Article

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