Anxiety Is Associated With Higher Levels of Global DNA Methylation and Altered Expression of Epigenetic and interleukin-6 Genes

Psychiatr Genet. 2015 Apr;25(2):71-8. doi: 10.1097/YPG.0000000000000055.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety / blood
  • Anxiety / enzymology
  • Anxiety / genetics*
  • Anxiety / metabolism
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / biosynthesis*
  • DNA (Cytosine-5-)-Methyltransferases / blood
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methylation*
  • Enhancer of Zeste Homolog 2 Protein
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / blood
  • Interleukin-6 / genetics*
  • Male
  • Manifest Anxiety Scale
  • Polycomb Repressive Complex 2 / biosynthesis*
  • Polycomb Repressive Complex 2 / blood
  • Polycomb Repressive Complex 2 / genetics

Substances

  • IL6 protein, human
  • Interleukin-6
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA methyltransferase 3A
  • DNA methyltransferase 3B
  • DNMT1 protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2