Digitala Vetenskapliga Arkivet

Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
HPA axis dysregulation is associated with differential methylation of CpG-sites in related genes
Univ Cyprus, Med Sch, CY-1678 Nicosia, Cyprus.;Umeå Univ, Dept Clin Sci Psychiat, Umeå, Sweden..
Umeå Univ, Dept Clin Sci Psychiat, Umeå, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Neuropaediat Unit, Stockholm, Sweden..
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Schiöth: Funktionell farmakologi.ORCID-id: 0000-0001-6377-0270
Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden..
Vise andre og tillknytning
2021 (engelsk)Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikkel-id 20134Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

DNA methylation shifts in Hypothalamic-pituitary-adrenal (HPA) axis related genes is reported in psychiatric disorders including hypersexual disorder. This study, comprising 20 dexamethasone suppression test (DST) non-suppressors and 73 controls, examined the association between the HPA axis dysregulation, shifts in DNA methylation of HPA axis related genes and importantly, gene expression. Individuals with cortisol level >= 138 nmol/l, after the low dose (0.5 mg) dexamethasone suppression test (DST) were classified as non-suppressors. Genome-wide methylation pattern, measured in whole blood using the EPIC BeadChip, investigated CpG sites located within 2000 bp of the transcriptional start site of key HPA axis genes, i.e.: CRH, CRHBP, CRHR-1, CRHR-2, FKBP5 and NR3C1. Regression models including DNA methylation M-values and the binary outcome (DST non-suppression status) were performed. Gene transcripts with an abundance of differentially methylated CpG sites were identified with binomial tests. Pearson correlations and robust linear regressions were performed between CpG methylation and gene expression in two independent cohorts. Six of 76 CpG sites were significantly hypermethylated in DST non-suppressors (nominal P < 0.05), associated with genes CRH, CRHR1, CRHR2, FKBP5 and NR3C1. NR3C1 transcript AJ877169 showed statistically significant abundance of probes differentially methylated by DST non-suppression status and correlated with DST cortisol levels. Further, methylation levels of cg07733851 and cg27122725 were positively correlated with gene expression levels of the NR3C1 gene. Methylation levels of cg08636224 (FKBP5) correlated with baseline cortisol and gene expression. Our findings revealed that DNA methylation shifts are involved in the altered mechanism of the HPA axis suggesting that new epigenetic targets should be considered behind psychiatric disorders.

sted, utgiver, år, opplag, sider
Springer Nature Springer Nature, 2021. Vol. 11, nr 1, artikkel-id 20134
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-458317DOI: 10.1038/s41598-021-99714-xISI: 000706395800055PubMedID: 34635736OAI: oai:DiVA.org:uu-458317DiVA, id: diva2:1609870
Forskningsfinansiär
Swedish Research Council, 202001183Tilgjengelig fra: 2021-11-09 Laget: 2021-11-09 Sist oppdatert: 2024-01-15bibliografisk kontrollert

Open Access i DiVA

fulltekst(1378 kB)117 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 1378 kBChecksum SHA-512
3fbfe44906eb7c91cf4d5a77004a304137668d452aa539e6660f01937a5f51b68cb999ec61a7c7e8d51cfaf8f2e00d91a0712875cc631519a6f706ad79b5c5ce
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekstPubMed

Søk i DiVA

Av forfatter/redaktør
Ciuculete, Diana-MariaSchiöth, Helgi B.
Av organisasjonen
I samme tidsskrift
Scientific Reports

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 117 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 100 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf