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000140563 037__ $$aDZNE-2020-06885
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000140563 1001_ $$aKlinger-König, Johanna$$b0
000140563 245__ $$aMethylation of the FKBP5 gene in association with FKBP5 genotypes, childhood maltreatment and depression.
000140563 260__ $$aBasingstoke$$bNature Publishing Group71819$$c2019
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000140563 264_1 $$2Crossref$$3print$$bSpringer Science and Business Media LLC$$c2019-04-01
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000140563 520__ $$aDNA methylation of the FKBP5 gene is assumed to alter FKBP5 expression and hence the synthesis of the FK506 binding protein 51, a central element of a genomic negative feedback loop for glucocorticoid receptor signaling. The present study aimed to replicate and extend previously reported influences of FKBP5 genotypes, childhood maltreatment and depression on methylation levels of five CpG sites in intron 7 of the FKBP5 gene in a large population-based sample. Besides the single nucleotide polymorphism (SNP) rs1360780, associations of the FKBP5 methylation with 22 other, unlinked FKBP5 SNPs as well as associations between FKBP5 methylation levels and transcription levels were investigated. Using whole-blood methylation of 3965 subjects of the Study of Health in Pomerania (SHIP) reduced methylation levels in TT allele carriers of rs1360780 (OR = 0.975, p = .005) and currently depressed subjects (OR = 0.995, p = 0.005) were found. Further, an impact of two yet undescribed SNPs (rs6910300, rs7771727) on methylation levels was observed. However, main and interactive effects for childhood maltreatment and lifetime major depressive disorder observed in previous studies could not be replicated. Finally, FKBP5 methylation levels were not related to FKBP5 transcription levels in whole blood. Thus, the present study verified the associations of FKBP5 genotypes and state depression on the FKBP5 methylation levels of five CpG sites in intron 7. However, FKBP5 methylation of these five CpG sites could not be validated as a valuable clinical biomarker for biological long-term effects of childhood maltreatment or lifetime depression.
000140563 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
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000140563 650_7 $$0EC 5.2.1.-$$2NLM Chemicals$$aTacrolimus Binding Proteins
000140563 650_7 $$0EC 5.2.1.8$$2NLM Chemicals$$atacrolimus binding protein 5
000140563 650_2 $$2MeSH$$aAdult
000140563 650_2 $$2MeSH$$aAdult Survivors of Child Abuse: statistics & numerical data
000140563 650_2 $$2MeSH$$aAdverse Childhood Experiences: statistics & numerical data
000140563 650_2 $$2MeSH$$aAged
000140563 650_2 $$2MeSH$$aDNA Methylation: genetics
000140563 650_2 $$2MeSH$$aDepressive Disorder: epidemiology
000140563 650_2 $$2MeSH$$aDepressive Disorder: etiology
000140563 650_2 $$2MeSH$$aDepressive Disorder: genetics
000140563 650_2 $$2MeSH$$aFemale
000140563 650_2 $$2MeSH$$aFollow-Up Studies
000140563 650_2 $$2MeSH$$aGermany: epidemiology
000140563 650_2 $$2MeSH$$aHumans
000140563 650_2 $$2MeSH$$aMale
000140563 650_2 $$2MeSH$$aMiddle Aged
000140563 650_2 $$2MeSH$$aRegistries
000140563 650_2 $$2MeSH$$aTacrolimus Binding Proteins: genetics
000140563 650_2 $$2MeSH$$aYoung Adult
000140563 7001_ $$0P:(DE-HGF)0$$aHertel, Johannes$$b1
000140563 7001_ $$0P:(DE-2719)9001174$$aVan der Auwera, Sandra$$b2$$udzne
000140563 7001_ $$aFrenzel, Stefan$$b3
000140563 7001_ $$aPfeiffer, Liliane$$b4
000140563 7001_ $$aWaldenberger, Melanie$$b5
000140563 7001_ $$aGolchert, Janine$$b6
000140563 7001_ $$aTeumer, Alexander$$b7
000140563 7001_ $$aNauck, Matthias$$b8
000140563 7001_ $$aHomuth, Georg$$b9
000140563 7001_ $$aVölzke, Henry$$b10
000140563 7001_ $$0P:(DE-2719)2811781$$aGrabe, Hans J$$b11$$eLast author
000140563 77318 $$2Crossref$$3journal-article$$a10.1038/s41386-019-0319-6$$bSpringer Science and Business Media LLC$$d2019-01-23$$n5$$p930-938$$tNeuropsychopharmacology$$v44$$x0893-133X$$y2019
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