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    Anxiety is associated with higher levels of global DNA methylation and altered expression of epigenetic and interleukin-6 genes

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    URI
    http://hdl.handle.net/11287/593940
    Author
    Murphy, Therese M.
    O'Donovan, A.
    Mullins, N.
    O'Farrelly, C.
    McCann, A.
    Malone, K.
    Date
    2015-04-01
    Journal
    Psychiatric genetics
    Type
    Journal Article
    Research Support, Non-U.S. Gov't
    Publisher
    Wolters Kluwer
    DOI
    10.1097/YPG.0000000000000055
    Metadata
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    Abstract
    OBJECTIVES: Anxiety is associated with elevated levels of the inflammatory cytokine interleukin-6 (IL-6) and an increased risk for diseases with an inflammatory aetiology. In cancer, higher levels of IL-6 have been associated with increased expression of the epigenetic enzymes DNMT1 and Enhancer of Zeste Homolog 2 (EZH2). However, the relationship between IL-6 and DNA methyltransferases (DNMTs) and EZH2 expression has not previously been examined in anxious individuals. METHODS: Global DNA methylation levels were measured using the Methylflash Methylated DNA Quantification Kit and gene expression levels of the DNMT and EZH2 genes in anxious (n=25) and nonanxious individuals (n=22) were compared using quantitative real-time PCR. Specifically, we investigated whether global DNA methylation or aberrant expression of these genes was correlated with IL-6 mRNA and protein serum levels in anxious individuals. RESULTS: Anxious participants had significantly higher levels of global DNA methylation compared with controls (P=0.001). There were no differences in the mean mRNA expression levels of the DNMT1/3A/3B, EZH2 and IL-6 genes in anxious individuals compared with controls. However, the expression of DNMT1/3A, EZH2 and IL-6 genes increases with increasing Hospital Anxiety and Depression Scale-Anxiety scores in the anxious cohort only. Interestingly, IL-6 gene expression was correlated strongly with DNMT1/3A/3B and EZH2 expression, highlighting a potential relationship between IL-6 and important epigenetic regulatory enzymes. CONCLUSION: This study provides novel insight into the relationship between anxiety, epigenetics and IL-6. Moreover, our findings support the hypothesis that changes in DNA methylation profiles may contribute to the biology of anxiety.
    Citation
    Psychiatr Genet. 2015 Apr;25(2):71-8.
    Publisher URL
    http://www.ncbi.nlm.nih.gov/pubmed/25350786
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