Dataset Information

Methylation matters: FK506 binding protein 51 (FKBP5) methylation moderates the associations of FKBP5 genotype and resistant attachment with stress regulation.

ABSTRACT: The parent-child attachment relationship plays an important role in the development of the infant's stress regulation system. However, genetic and epigenetic factors such as FK506 binding protein 51 (FKBP5) genotype and DNA methylation have also been associated with hypothalamus-pituitary-adrenal axis functioning. In the current study, we examined how parent-child dyadic regulation works in concert with genetic and epigenetic aspects of stress regulation. We study the associations of attachment, extreme maternal insensitivity, FKBP5 single nucleotide polymorphism 1360780, and FKBP5 methylation, with cortisol reactivity to the Strange Situation Procedure in 298 14-month-old infants. The results indicate that FKBP5 methylation moderates the associations of FKBP5 genotype and resistant attachment with cortisol reactivity. We conclude that the inclusion of epigenetics in the field of developmental psychopathology may lead to a more precise picture of the interplay between genetic makeup and parenting in shaping stress reactivity.

SUBMITTER: Mulder RH

PROVIDER: S-EPMC5426551 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Methylation matters: FK506 binding protein 51 (FKBP5) methylation moderates the associations of FKBP5 genotype and resistant attachment with stress regulation.

Mulder Rosa H RH Rijlaarsdam Jolien J Luijk Maartje P C M MP Verhulst Frank C FC Felix Janine F JF Tiemeier Henning H Bakermans-Kranenburg Marian J MJ Van Ijzendoorn Marinus H MH

Development and psychopathology 20170501 2

The parent-child attachment relationship plays an important role in the development of the infant's stress regulation system. However, genetic and epigenetic factors such as FK506 binding protein 51 (FKBP5) genotype and DNA methylation have also been associated with hypothalamus-pituitary-adrenal axis functioning. In the current study, we examined how parent-child dyadic regulation works in concert with genetic and epigenetic aspects of stress regulation. We study the associations of attachment, ...[more]

PMID: 28401840

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Project description:BackgroundSleep disturbance is an outcome of multiple factors including environmental and genetic influences. Job stress, a complex environmental factor, likely affects sleep quality, significantly reducing the quality of life of workers. Additionally, FK506 binding protein 51 (FKBP5) may be a pathogenic factor for sleep disturbance as it regulates hypothalamic-pituitary-adrenal (HPA) axis activity, where HPA axis has been found to be involved in the regulation mechanism of sleep and stress response.ObjectivesThe main aim of this study was to investigate the association between job stress and FKBP5 gene polymorphism as well as their interaction with sleep disturbance in Chinese workers; to date, these relationships have not been explored.MethodsThis is a cross-sectional study. A total of 675 railway workers (53.8% male) completed a short Effort-Reward Imbalance questionnaire and the Pittsburgh Sleep Quality Index. The SNaPshot single nucleotide polymorphism (SNP) assay was carried out by screening for FKBP5 SNPs in every participant. Generalized multifactor dimensionality reduction (GMDR) was used to identify the strongest G×E interaction combination.ResultsThe findings showed that job stress was significantly associated with sleep disturbance; specifically, scores on the PSQI subscales (sleep disturbance, sleep medication, and daytime dysfunction) exhibited significant differences between the two job stress groups (X2 = 18.10, p = 0.01). Additionally, the FKBP5 SNP rs1360780-TT (adjusted odds ratio [AOR] = 4.98, 95% confidence interval [CI] = 2.80-8.84) and rs3800373-CC genotype (AOR = 2.06, CI = 1.10-3.86) were associated with an increased risk of sleep disturbance. Job stress and rs1360780 and rs3800373 variants showed a high-dimensional interaction with sleep disturbance as determined by the GMDR model.ConclusionThe FKBP5 gene may increase susceptibility to job stress and result in sleep disturbance, especially in the presence of negative work-related events. These findings contribute to the field of sleep disturbance prevention and treatment.

Project description:BackgroundDisruption of the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system associated with the stress response, has been hypothesized to contribute to obesity development. This may be mediated through epigenetic modulation of HPA axis-regulatory genes in response to metabolic stressors. The aim of this study was to investigate adipose tissue depot-specific DNA methylation differences in the glucocorticoid receptor (GR) and its co-chaperone, FK506-binding protein 51 kDa (FKBP5), both key modulators of the HPA axis.MethodsAbdominal subcutaneous adipose tissue (ASAT) and gluteal subcutaneous adipose tissue (GSAT) biopsies were obtained from a sample of 27 obese and 27 normal weight urban-dwelling South African women. DNA methylation and gene expression were measured by pyrosequencing and quantitative real-time PCR, respectively. Spearman's correlation coefficients, orthogonal partial least-squares discriminant analysis and multivariable linear regression were performed to evaluate the associations between DNA methylation, messenger RNA (mRNA) expression and key indices of obesity and metabolic dysfunction.ResultsTwo CpG dinucleotides within intron 7 of FKBP5 were hypermethylated in both ASAT and GSAT in obese compared to normal weight women, while no differences in GR methylation were observed. Higher percentage methylation of the two FKBP5 CpG sites correlated with adiposity (body mass index and waist circumference), insulin resistance (homeostasis model for insulin resistance, fasting insulin and plasma adipokines) and systemic inflammation (c-reactive protein) in both adipose depots. GR and FKBP5 mRNA levels were lower in GSAT, but not ASAT, of obese compared to normal weight women. Moreover, FKBP5 mRNA levels were inversely correlated with DNA methylation and positively associated with adiposity, metabolic and inflammatory parameters.ConclusionsThese findings associate dysregulated FKBP5 methylation and mRNA expression with obesity and insulin resistance in South African women. Additional studies are required to assess the longitudinal association of FKBP5 with obesity and associated co-morbidities in large population-based samples.

Dataset Information

Methylation matters: FK506 binding protein 51 (FKBP5) methylation moderates the associations of FKBP5 genotype and resistant attachment with stress regulation.

Publications

Methylation matters: FK506 binding protein 51 (FKBP5) methylation moderates the associations of FKBP5 genotype and resistant attachment with stress regulation.

Similar Datasets

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