P2RX7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms.
The P2X purinoceptor 7 (P2RX7) mediates inflammatory microglial responses and is implicated in neuroimmune mechanisms of depression and neurodegenerative disorders. A number of studies suggest that psychosocial stress may precipitate depression through immune activation. Genetic association studies...
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2021
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oai:doaj.org-article:6a53842c27204f458916cea46a0bd37e2021-12-02T20:07:11ZP2RX7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms.1932-620310.1371/journal.pone.0252766https://doaj.org/article/6a53842c27204f458916cea46a0bd37e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252766https://doaj.org/toc/1932-6203The P2X purinoceptor 7 (P2RX7) mediates inflammatory microglial responses and is implicated in neuroimmune mechanisms of depression and neurodegenerative disorders. A number of studies suggest that psychosocial stress may precipitate depression through immune activation. Genetic association studies of P2RX7 variants with depression have been inconclusive. However, nearly all studies have focused on only one single-nucleotide polymorphism (SNP) and have not considered interaction with psychosocial stress. We investigated the effect of several variations in P2RX7 gene using a clumping method in interaction with early adversities and recent stress on depression severity. 1752 subjects provided information on childhood adversities, recent life events, and current depression severity. Participants were genotyped for 681 SNPs in the P2RX7 gene, 335 of them passed quality control and were entered into linear regression models followed by a clumping procedure for main effect and interactions. No significant main effect was observed. Rs74892325 emerged as a top SNP for interaction with childhood adversities and rs61953400 for interaction with recent life events. Our study is the first to investigate several variants in the P2RX7 gene and in interaction with two types of stress, extending our understanding of neuroinflammation in depression, and supporting that the majority of genes influence depression by enhancing sensitivity to stressors.Zsuliet KristofNora EszlariSara SutoriZsofia GalDora TorokDaniel BaksaPeter PetschnerBeata SperlaghIan M AndersonJohn Francis William DeakinGabriella JuhaszGyorgy BagdyXenia GondaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0252766 (2021) |
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Medicine R Science Q |
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Medicine R Science Q Zsuliet Kristof Nora Eszlari Sara Sutori Zsofia Gal Dora Torok Daniel Baksa Peter Petschner Beata Sperlagh Ian M Anderson John Francis William Deakin Gabriella Juhasz Gyorgy Bagdy Xenia Gonda P2RX7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms. |
| description |
The P2X purinoceptor 7 (P2RX7) mediates inflammatory microglial responses and is implicated in neuroimmune mechanisms of depression and neurodegenerative disorders. A number of studies suggest that psychosocial stress may precipitate depression through immune activation. Genetic association studies of P2RX7 variants with depression have been inconclusive. However, nearly all studies have focused on only one single-nucleotide polymorphism (SNP) and have not considered interaction with psychosocial stress. We investigated the effect of several variations in P2RX7 gene using a clumping method in interaction with early adversities and recent stress on depression severity. 1752 subjects provided information on childhood adversities, recent life events, and current depression severity. Participants were genotyped for 681 SNPs in the P2RX7 gene, 335 of them passed quality control and were entered into linear regression models followed by a clumping procedure for main effect and interactions. No significant main effect was observed. Rs74892325 emerged as a top SNP for interaction with childhood adversities and rs61953400 for interaction with recent life events. Our study is the first to investigate several variants in the P2RX7 gene and in interaction with two types of stress, extending our understanding of neuroinflammation in depression, and supporting that the majority of genes influence depression by enhancing sensitivity to stressors. |
| format |
article |
| author |
Zsuliet Kristof Nora Eszlari Sara Sutori Zsofia Gal Dora Torok Daniel Baksa Peter Petschner Beata Sperlagh Ian M Anderson John Francis William Deakin Gabriella Juhasz Gyorgy Bagdy Xenia Gonda |
| author_facet |
Zsuliet Kristof Nora Eszlari Sara Sutori Zsofia Gal Dora Torok Daniel Baksa Peter Petschner Beata Sperlagh Ian M Anderson John Francis William Deakin Gabriella Juhasz Gyorgy Bagdy Xenia Gonda |
| author_sort |
Zsuliet Kristof |
| title |
P2RX7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms. |
| title_short |
P2RX7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms. |
| title_full |
P2RX7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms. |
| title_fullStr |
P2RX7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms. |
| title_full_unstemmed |
P2RX7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms. |
| title_sort |
p2rx7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/6a53842c27204f458916cea46a0bd37e |
| work_keys_str_mv |
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| _version_ |
1718375308602638336 |