DNA methylation of FKBP5 in South African women : associations with obesity and insulin resistance

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dc.contributor.authorWillmer, Tarrynen_ZA
dc.contributor.authorGoedecke, Julia H.en_ZA
dc.contributor.authorDias, Stephanieen_ZA
dc.contributor.authorLouw, Johanen_ZA
dc.contributor.authorPheiffer, Carmenen_ZA
dc.date.accessioned2020-10-12T10:41:17Z
dc.date.available2020-10-12T10:41:17Z
dc.date.issued2020-09-21
dc.date.updated2020-09-27T03:25:29Z
dc.descriptionCITATION: Willmer, T., et al. 2020. DNA methylation of FKBP5 in South African women : associations with obesity and insulin resistance. Clinical Epigenetics, 12:141, doi:10.1186/s13148-020-00932-3.
dc.descriptionThe original publication is available at https://clinicalepigeneticsjournal.biomedcentral.com
dc.description.abstractBackground: Disruption 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. Methods: Abdominal 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. Results: Two 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. Conclusions: These 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.
dc.description.urihttps://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00932-3
dc.description.versionPublisher's version
dc.format.extent15 pagesen_ZA
dc.identifier.citationWillmer, T., et al. 2020. DNA methylation of FKBP5 in South African women : associations with obesity and insulin resistance. Clinical Epigenetics, 12:141, doi:10.1186/s13148-020-00932-3
dc.identifier.issn1868-7083 (online)
dc.identifier.issn1868-7075 (print)
dc.identifier.otherdoi:10.1186/s13148-020-00932-3
dc.identifier.urihttp://hdl.handle.net/10019.1/108882
dc.language.isoen_ZAen_ZA
dc.publisherBMC (part of Springer Nature)en_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectObesityen_ZA
dc.subjectDNA -- Methylationen_ZA
dc.subjectInsulin resistanceen_ZA
dc.subjectGlucocorticoid receptoren_ZA
dc.subjectAdipose tissueen_ZA
dc.titleDNA methylation of FKBP5 in South African women : associations with obesity and insulin resistanceen_ZA
dc.typeArticleen_ZA
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