Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness.
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....
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184832&type=printable |
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| author | Yang Chen Joel N Meyer Helene Z Hill Gudrun Lange Michael R Condon Jacquelyn C Klein Duncan Ndirangu Michael J Falvo |
| author_facet | Yang Chen Joel N Meyer Helene Z Hill Gudrun Lange Michael R Condon Jacquelyn C Klein Duncan Ndirangu Michael J Falvo |
| author_sort | Yang Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-69ac5875f505402c87bb99bc6e040f91 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-69ac5875f505402c87bb99bc6e040f912025-08-20T03:04:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018483210.1371/journal.pone.0184832Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness.Yang ChenJoel N MeyerHelene Z HillGudrun LangeMichael R CondonJacquelyn C KleinDuncan NdiranguMichael J FalvoGulf 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184832&type=printable |
| spellingShingle | Yang Chen Joel N Meyer Helene Z Hill Gudrun Lange Michael R Condon Jacquelyn C Klein Duncan Ndirangu Michael J Falvo Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness. PLoS ONE |
| title | Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness. |
| title_full | Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness. |
| title_fullStr | Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness. |
| title_full_unstemmed | Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness. |
| title_short | Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness. |
| title_sort | role of mitochondrial dna damage and dysfunction in veterans with gulf war illness |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184832&type=printable |
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