Differential methylation of the oxytocin receptor gene in patients with anorexia nervosa: a pilot study

PLoS One. 2014 Feb 11;9(2):e88673. doi: 10.1371/journal.pone.0088673. eCollection 2014.

Abstract

Background and aim: Recent studies in patients with anorexia nervosa suggest that oxytocin may be involved in the pathophysiology of anorexia nervosa. We examined whether there was evidence of variation in methylation status of the oxytocin receptor (OXTR) gene in patients with anorexia nervosa that might account for these findings.

Methods: We analyzed the methylation status of the CpG sites in a region from the exon 1 to the MT2 regions of the OXTR gene in buccal cells from 15 patients and 36 healthy women using bisulfite sequencing. We further examined whether methylation status was associated with markers of illness severity or form.

Results: We identified six CpG sites with significant differences in average methylation levels between the patient and control groups. Among the six differentially methylated CpG sites, five showed higher than average methylation levels in patients than those in the control group (64.9-88.8% vs. 6.6-45.0%). The methylation levels of these five CpG sites were negatively associated with body mass index (BMI). BMI, eating disorders psychopathology, and anxiety were identified in a regression analysis as factors affecting the methylation levels of these CpG sites with more variation accounted for by BMI.

Conclusions: Epigenetic misregulation of the OXTR gene may be implicated in anorexia nervosa, which may either be a mechanism linking environmental adversity to risk or may be a secondary consequence of the illness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anorexia Nervosa / genetics*
  • Body Mass Index
  • Case-Control Studies
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Humans
  • Pilot Projects
  • Receptors, Oxytocin / genetics*
  • Receptors, Oxytocin / metabolism
  • Risk
  • Sequence Analysis, DNA
  • Sulfites / chemistry
  • Surveys and Questionnaires
  • Young Adult

Substances

  • OXTR protein, human
  • Receptors, Oxytocin
  • Sulfites
  • hydrogen sulfite

Grants and funding

This study was supported under the framework of the International Cooperation Program managed by the National Research Foundation of Korea (2011-0030914) to YK. The Swiss Anorexia Nervosa Foundation supported the work of JT in part. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. JT received salary support from the National Institute for Health Research (NIHR), Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.