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

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.

Association between academic pressure, NR3C1 gene methylation, and anxiety symptoms among Chinese adolescents: a nested case-control study

“…However, relatively few studies have evaluated these associations. Additionally, few related studies estimating the associations of NR3C1 methylation with stress exposure and anxiety-related outcomes have accounted for other important confounders other than sex and age [ 29 , 30 ], such as cortisol and body mass index (BMI), which have also been reported to be associated with anxiety and NR3C1 DNA methylation [ 31 , 32 ].…”