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Expression of DNA repair genes and its relevance for DNA repair in peripheral immune cells of patients with posttraumatic stress disorder

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2022

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Scientific reports. Springer Nature. 2022, 12(1), 18641. eISSN 2045-2322. Available under: doi: 10.1038/s41598-022-22001-w

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Posttraumatic stress disorder (PTSD) involves elevated levels of cellular oxidative stress which jeopardizes the integrity of essential cell compartments. Previously, we demonstrated higher levels of DNA lesions in peripheral blood mononuclear cells (PBMCs) in PTSD. Retaining vital levels of DNA integrity requires cells to mobilize compensatory efforts in elevating their DNA-repair capacity. Accordingly, we hypothesized to find increased expression rates of the DNA-repair genes X-ray repair cross complementing 1 (XRCC1), poly (ADP-ribose) polymerase 1 (PARP1), and polymerase β (Polβ) in PBMCs of PTSD patients as compared to controls, leading to functionally relevant changes in DNA-repair kinetics. In a cohort of 14 refugees with PTSD and 15 without PTSD, we found significantly higher XRCC1 expression in PTSD patients than controls (U = 161.0, p = 0.009, Cohen's r = 0.49), and positive correlations between the severity of PTSD symptoms and the expression of XRCC1 (rS = 0.57, p = 0.002) and PARP1 (rS = 0.43, p = 0.022). Higher XRCC1 (F = 2.39, p = 0.010, η2p = 0.10) and PARP1 (F = 2.15, p = 0.022, η2p = 0.09) expression accounted for slower repair of experimentally X-ray irradiation-induced DNA damage, highlighting the possible physiological relevance of altered DNA-repair gene expression in PTSD. Our study provides first evidence for a compensatory regulation of DNA-repair mechanisms in PTSD. We discuss the implications of increased DNA damage and altered DNA-repair mechanisms in immune senescence, premature aging, and increased physical morbidity in PTSD.

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570 Biowissenschaften, Biologie

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ISO 690BEHNKE, Alexander, Matthias MACK, Judy FIERES, Markus CHRISTMANN, Alexander BÜRKLE, Maria MORENO-VILLANUEVA, Iris-Tatjana KOLASSA, 2022. Expression of DNA repair genes and its relevance for DNA repair in peripheral immune cells of patients with posttraumatic stress disorder. In: Scientific reports. Springer Nature. 2022, 12(1), 18641. eISSN 2045-2322. Available under: doi: 10.1038/s41598-022-22001-w
BibTex
@article{Behnke2022-11-04Expre-59380,
  year={2022},
  doi={10.1038/s41598-022-22001-w},
  title={Expression of DNA repair genes and its relevance for DNA repair in peripheral immune cells of patients with posttraumatic stress disorder},
  number={1},
  volume={12},
  journal={Scientific reports},
  author={Behnke, Alexander and Mack, Matthias and Fieres, Judy and Christmann, Markus and Bürkle, Alexander and Moreno-Villanueva, Maria and Kolassa, Iris-Tatjana},
  note={Article Number: 18641}
}
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    <dcterms:abstract xml:lang="eng">Posttraumatic stress disorder (PTSD) involves elevated levels of cellular oxidative stress which jeopardizes the integrity of essential cell compartments. Previously, we demonstrated higher levels of DNA lesions in peripheral blood mononuclear cells (PBMCs) in PTSD. Retaining vital levels of DNA integrity requires cells to mobilize compensatory efforts in elevating their DNA-repair capacity. Accordingly, we hypothesized to find increased expression rates of the DNA-repair genes X-ray repair cross complementing 1 (XRCC1), poly (ADP-ribose) polymerase 1 (PARP1), and polymerase β (Polβ) in PBMCs of PTSD patients as compared to controls, leading to functionally relevant changes in DNA-repair kinetics. In a cohort of 14 refugees with PTSD and 15 without PTSD, we found significantly higher XRCC1 expression in PTSD patients than controls (U = 161.0, p = 0.009, Cohen's r = 0.49), and positive correlations between the severity of PTSD symptoms and the expression of XRCC1 (rS = 0.57, p = 0.002) and PARP1 (rS = 0.43, p = 0.022). Higher XRCC1 (F = 2.39, p = 0.010, η2p = 0.10) and PARP1 (F = 2.15, p = 0.022, η2p = 0.09) expression accounted for slower repair of experimentally X-ray irradiation-induced DNA damage, highlighting the possible physiological relevance of altered DNA-repair gene expression in PTSD. Our study provides first evidence for a compensatory regulation of DNA-repair mechanisms in PTSD. We discuss the implications of increased DNA damage and altered DNA-repair mechanisms in immune senescence, premature aging, and increased physical morbidity in PTSD.</dcterms:abstract>
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