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

2.50
Hdl Handle:
http://hdl.handle.net/11287/593940
Title:
Anxiety is associated with higher levels of global DNA methylation and altered expression of epigenetic and interleukin-6 genes
Authors:
Murphy, Therese M.; O'Donovan, A.; Mullins, N.; O'Farrelly, C.; McCann, A.; Malone, K.
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:
Wolters Kluwer
Journal:
Psychiatric genetics
Issue Date:
1-Apr-2015
URI:
http://hdl.handle.net/11287/593940
DOI:
10.1097/YPG.0000000000000055
PubMed ID:
25350786
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/25350786
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1473-5873
Appears in Collections:
2015 RD&E publications; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorMurphy, Therese M.en
dc.contributor.authorO'Donovan, A.en
dc.contributor.authorMullins, N.en
dc.contributor.authorO'Farrelly, C.en
dc.contributor.authorMcCann, A.en
dc.contributor.authorMalone, K.en
dc.date.accessioned2016-01-19T12:37:40Zen
dc.date.available2016-01-19T12:37:40Zen
dc.date.issued2015-04-01en
dc.identifier.citationPsychiatr Genet. 2015 Apr;25(2):71-8.en
dc.identifier.issn1473-5873en
dc.identifier.pmid25350786en
dc.identifier.doi10.1097/YPG.0000000000000055en
dc.identifier.urihttp://hdl.handle.net/11287/593940en
dc.description.abstractOBJECTIVES: 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.en
dc.language.isoengen
dc.publisherWolters Kluweren
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/25350786en
dc.titleAnxiety is associated with higher levels of global DNA methylation and altered expression of epigenetic and interleukin-6 genesen
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalPsychiatric geneticsen

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