Methylation of the glucocorticoid receptor gene (NR3C1) in dyads mother-child exposed to intimate partner violence in Cameroon: Association with anxiety symptoms

PLoS One. 2023 Apr 6;18(4):e0273602. doi: 10.1371/journal.pone.0273602. eCollection 2023.

Abstract

Background: The glucocorticoid receptor (GR), which is encoded by the NR3C1 (Nuclear Receptor Subfamily 3 Group C Member 1) gene plays an important role in the modulation of the hypothalamic-pituitary-adrenal (HPA) axis activity by providing feedback regulation which allows termination of the stress response. Little is known about epigenetic programming at the level of NGFI-A (nerve growth factor-inducible protein A) putative binding site (CpG) of the NR3C1 exon 1F in dyads mother-child exposed to intimate partner violence (IPV) more specifically in an unstudied region such as the sub-Saharan Africa where levels of violence are very high.

Objective: Examine NR3C1 exon 1F methylation in response to IPV and possible association with cortisol concentration and mental health.

Method: We recruited 20 mother-child dyads exposed to IPV and a control group of 20 mother-child dyads not exposed to IPV. We administered self-reported questionnaires to measure mother's mental health and collected saliva samples for cortisol dosage and bisulfite sequencing of DNA methylation.

Results: Regarding the mothers, our results showed a significant difference in methylation level at CpG 16-21 sites of the NR3C1 exon 1F promoter region between the groups. In the exposed group as compared to the control group, there was a significant positive association between the level of methylation at CpG 16-21 sites and mother's mental health in particular anxiety symptoms. However, we did not find any significant correlation between methylation level and cortisol concentration. In children, we did not find any significant results.

Conclusion: This study highlights a NGFI-A putative binding site (CpG 16-21) that is more methylated in mothers exposed to IPV and which may have the potential to confer vulnerability for psychopathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anxiety / genetics
  • Cameroon
  • CpG Islands / genetics
  • DNA Methylation
  • Female
  • Glucocorticoids*
  • Humans
  • Hydrocortisone / metabolism
  • Intimate Partner Violence*
  • Mother-Child Relations
  • Promoter Regions, Genetic
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism

Substances

  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Hydrocortisone
  • NR3C1 protein, human

Grants and funding

This research was funded by the Swiss Government Excellence Scholarships (2018.0801) and the Swiss National Science Foundation (SNSF) (P1FRP1_199872) awarded to the first author. This work was also supported by the University of Fribourg Research Pool. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.