Associations of FKBP5 polymorphisms and methylation and parenting style with depressive symptoms among Chinese adolescents

Abstract

Background Genetic factors may interplay with environmental stressors to contribute to risks of depressive symptoms. This study aimed to investigate the association of FKBP5 polymorphisms and DNA methylation with depressive symptoms among Chinese adolescents, considering the role of parenting style. Methods This study used a nested case-control study design based on a cohort study, and the case (n = 120) and control groups (n = 118) were matched with age. Depressive symptoms, parenting style, and other demographics were measured. Fourteen potential polymorphisms and one promoter region in the FKBP5 gene were selected for genotyping and methylation analysis. Results In the adjusted models, a significant association between FKBP5 rs7757037 and depressive symptoms was found in the codominant model (AG vs. GG; adjusted odds ratio [AOR] = 2.56, 95% CI = 1.13–5.78) and dominant model (AA+AG vs. GG; AOR = 2.38, 95% CI = 1.11–5.120); rs2817032 and rs2817035 polymorphisms were associated with depressive symptoms in the codominant model and dominant model. Significant interactions between rs7757037 and the father’s parenting style were found in the codominant model (P = 0.043) and dominant model (P = 0.043), but the gene-environment interactions were not significant after correcting for multiple testing. Moreover, the significant main effects of FKBP5 methylation status on depressive symptoms were not observed, and there was no significant interaction between FKBP5 methylation status and parenting style on depressive symptoms. Conclusions Further studies are required to confirm the effect of FKBP5 polymorphisms and methylation as well as their interactions with parenting styles in larger samples.

Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery

“…The G allele, with higher frequencies in the population, was linked with the risk of bipolar disorder (30). In lupus patients, the FKBP5 gene variant rs7757037 was linked to depression (162), but no similar finding was achieved in an adolescent Chinese population in which the association between depressive symptoms and parenting styles was measured (163).…”

The role of DNA methylation in progression of neurological disorders and neurodegenerative diseases as well as the prospect of using DNA methylation inhibitors as therapeutic agents for such disorders

“…Depressive symptoms in adolescence have long-term consequences for brain development and can cause severe social and educational problems. Furthermore, depression is linked to cerebrovascular diseases such as stroke ( Guo et al, 2021 , Xiang et al, 2021 ). Major depressive disorder (MDD) is a complex, debilitating psychiatric condition with a high prevalence of 3.63%.…”

“…Exposure to stress can modify DNA methylation patterns and affects brain plasticity and emotion ( Reszka et al, 2021 ). One of the main neurobiological mechanisms of depression is dysregulated and dysfunctional stress response system (such as hypothalamic-pituitary-adrenal (HPA) axis activity and glucocorticoid receptor (GR) sensitivity) to show the adaptive change ( Guo et al, 2021 ). Moreover, prenatal depressive symptoms might influence fetal epigenetic programming ( Kallak et al, 2021 ).…”

“…Exposure to stress results in the modification of DNA methylation in several genes associated with depression, including the glucocorticoid receptor (NR3C1 or GR), mineralocorticoid receptor (NR3C2 or MR), corticotrophin-releasing hormone receptor 1 (CRHR1), serotonin transporter (SLC6A4 or 5-HTT), brain-derived neurotrophic factor (BDNF), and FK506-binding protein 5 (FKBP5) ( Borçoi et al, 2021 , Drzymalla et al, 2021 , Ding and Dai, 2019 ). Different studies have reported the significant relationship between alteration in DNA methylation of FKBP5 with depressive symptoms ( Guo et al, 2021 , Han et al, 2017 , Höhne et al, 2015 ). These alterations in gene expression may lead to significant modifications in neural and behavioral functions ( Sales et al, 2021 ).…”

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

“…Several types of stressful life events have been frequently reported to alter the methylation of these genes [ 19 , 21 ]. Although our prior works did not observe a significant association between FKBP5 methylation and anxiety symptoms [ 22 , 23 ], the NR3C1 gene, which encodes GR and regulates the release of glucocorticoids in the HPA axis [ 24 ], also merits attention. Previous studies have demonstrated that hypermethylation of the NR3C1 gene is associated with internalizing psychopathologies such as anxiety or depression [ 25 , 26 ].…”