Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/106862
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dc.contributor.authorRichter, Gesa M.-
dc.contributor.authorKruppa, Jochen-
dc.contributor.authorMunz, Matthias-
dc.contributor.authorWiehe, Ricarda-
dc.contributor.authorHäsler, Robert-
dc.contributor.authorFranke, Andre-
dc.contributor.authorMartins, Orlando-
dc.contributor.authorJockel-Schneider, Yvonne-
dc.contributor.authorBruckmann, Corinna-
dc.contributor.authorDommisch, Henrik-
dc.contributor.authorSchaefer, Arne S.-
dc.date.accessioned2023-04-27T11:00:43Z-
dc.date.available2023-04-27T11:00:43Z-
dc.date.issued2019-07-22-
dc.identifier.issn1868-7075pt
dc.identifier.issn1868-7083pt
dc.identifier.urihttps://hdl.handle.net/10316/106862-
dc.description.abstractBackground: The oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking. Results: Ex vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1; best p = 5.5 × 10−8) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p = 5.9 × 10−9). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1, with p = 4.0 × 10−10. RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers (p = 2.2 × 10−14), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR. In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1. Conclusion: This study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa.pt
dc.language.isoengpt
dc.publisherSpringer Naturept
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subjectEWASpt
dc.subjectMethylationpt
dc.subjectExpressionpt
dc.subjectMasticatory mucosapt
dc.subjectCYP1B1pt
dc.subjectAHRRpt
dc.subjectCytochrome P 450 pathwaypt
dc.subjectOSCCpt
dc.subjectSmokingpt
dc.subject.meshAdultpt
dc.subject.meshBasic Helix-Loop-Helix Transcription Factorspt
dc.subject.meshCase-Control Studiespt
dc.subject.meshCigarette Smokingpt
dc.subject.meshCpG Islandspt
dc.subject.meshCytochrome P-450 CYP1B1pt
dc.subject.meshDNA Methylationpt
dc.subject.meshEpigenesis, Geneticpt
dc.subject.meshEpigenomicspt
dc.subject.meshFemalept
dc.subject.meshGene Expression Profilingpt
dc.subject.meshGenome-Wide Association Studypt
dc.subject.meshHealthy Volunteerspt
dc.subject.meshHumanspt
dc.subject.meshMalept
dc.subject.meshMiddle Agedpt
dc.subject.meshMouth Mucosapt
dc.subject.meshRepressor Proteinspt
dc.subject.meshSequence Analysis, RNApt
dc.subject.meshSmokerspt
dc.subject.meshUp-Regulationpt
dc.subject.meshExome Sequencingpt
dc.titleA combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokerspt
dc.typearticle-
degois.publication.firstPage105pt
degois.publication.issue1pt
degois.publication.titleClinical Epigeneticspt
dc.peerreviewedyespt
dc.identifier.doi10.1186/s13148-019-0697-ypt
degois.publication.volume11pt
dc.date.embargo2019-07-22*
uc.date.periodoEmbargo0pt
item.cerifentitytypePublications-
item.languageiso639-1en-
item.fulltextCom Texto completo-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypearticle-
Appears in Collections:FMUC Med. Dentária - Artigos em Revistas Internacionais
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