A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers.
Adult
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Case-Control Studies
Cigarette Smoking
/ adverse effects
CpG Islands
Cytochrome P-450 CYP1B1
/ genetics
DNA Methylation
/ drug effects
Epigenesis, Genetic
Epigenomics
/ methods
Female
Gene Expression Profiling
/ methods
Genome-Wide Association Study
Healthy Volunteers
Humans
Male
Middle Aged
Mouth Mucosa
/ chemistry
Repressor Proteins
/ genetics
Sequence Analysis, RNA
Smokers
Up-Regulation
Exome Sequencing
AHRR
CYP1B1
Cytochrome P 450 pathway
EWAS
Expression
Masticatory mucosa
Methylation
OSCC
Smoking
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
22 07 2019
22 07 2019
Historique:
received:
23
01
2019
accepted:
18
06
2019
entrez:
24
7
2019
pubmed:
25
7
2019
medline:
27
6
2020
Statut:
epublish
Résumé
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. 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 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.
Sections du résumé
BACKGROUND
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
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.
Identifiants
pubmed: 31331382
doi: 10.1186/s13148-019-0697-y
pii: 10.1186/s13148-019-0697-y
pmc: PMC6647091
doi:
Substances chimiques
AHRR protein, human
0
Basic Helix-Loop-Helix Transcription Factors
0
Repressor Proteins
0
CYP1B1 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP1B1
EC 1.14.14.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105Références
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
Epigenetics. 2015;10(12):1156-65
pubmed: 26829059
Bioinformatics. 2005 May 1;21(9):2067-75
pubmed: 15657102
Hum Genet. 2013 Sep;132(9):1027-37
pubmed: 23657504
Biomarkers. 2018 Nov;23(7):625-639
pubmed: 29771158
F1000Res. 2015 Dec 30;4:1521
pubmed: 26925227
J Dent Res. 1989 Sep;68(9):1345-9
pubmed: 2476469
Nat Genet. 2013 Oct;45(10):1113-20
pubmed: 24071849
Am J Respir Cell Mol Biol. 2015 Aug;53(2):246-54
pubmed: 25517428
Cancer Res. 2004 Sep 15;64(18):6805-13
pubmed: 15375000
Clin Epigenetics. 2015 Oct 16;7:113
pubmed: 26478754
JAMA Oncol. 2015 Jul;1(4):476-85
pubmed: 26181258
Bioinformatics. 2012 Mar 15;28(6):882-3
pubmed: 22257669
Am J Med Genet B Neuropsychiatr Genet. 2012 Mar;159B(2):141-51
pubmed: 22232023
Oncotarget. 2017 Jun 13;8(24):39087-39100
pubmed: 28388569
Clin Dermatol. 2000 Sep-Oct;18(5):499-511
pubmed: 11134845
J Clin Endocrinol Metab. 2002 Feb;87(2):666-74
pubmed: 11836302
PLoS One. 2013 May 17;8(5):e63812
pubmed: 23691101
Curr Protoc Neurosci. 2016 Oct 3;77:9.54.1-9.54.10
pubmed: 27696362
Hum Mol Genet. 2013 Mar 1;22(5):843-51
pubmed: 23175441
Environ Health Perspect. 2012 Oct;120(10):1425-31
pubmed: 22851337
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Clin Periodontol. 2005;32 Suppl 6:210-3
pubmed: 16128839
Cancer Res. 1997 Jul 15;57(14):3026-31
pubmed: 9230218
Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):11115-20
pubmed: 23776235
BMJ. 1997 Oct 4;315(7112):841-6
pubmed: 9353503
Nat Biotechnol. 2010 Oct;28(10):1057-68
pubmed: 20944598
Epigenomics. 2016 May;8(5):599-618
pubmed: 26864933
Epigenetics. 2014 Oct;9(10):1382-96
pubmed: 25424692
Curr Opin Toxicol. 2017 Feb;2:109-119
pubmed: 28971163
Methods Mol Biol. 2015;1238:51-63
pubmed: 25421654
Clin Epigenetics. 2018 Oct 20;10(1):126
pubmed: 30342560
Genome Biol. 2016 Oct 7;17(1):208
pubmed: 27717381
Epigenetics. 2012 Nov;7(11):1331-8
pubmed: 23070629
BMC Bioinformatics. 2009 May 27;10:161
pubmed: 19473525
N Engl J Med. 1994 Feb 10;330(6):387-92
pubmed: 8284003
Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10143-8
pubmed: 15210990
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9
pubmed: 16009939
Bioinformatics. 2016 Dec 15;32(24):3836-3838
pubmed: 27540268
Hum Mol Genet. 2015 Apr 15;24(8):2349-59
pubmed: 25556184
PLoS Genet. 2011 Apr;7(4):e1002033
pubmed: 21490707
PLoS One. 2011;6(11):e27914
pubmed: 22114726
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
J Natl Cancer Inst Monogr. 2001;(29):7-15
pubmed: 11694559
BMC Bioinformatics. 2010 Nov 30;11:587
pubmed: 21118553
PLoS One. 2016 May 12;11(5):e0155554
pubmed: 27171005
N Engl J Med. 2013 Jan 24;368(4):351-64
pubmed: 23343064
Genome Biol. 2014 Dec 03;15(12):503
pubmed: 25599564
Oncotarget. 2017 Mar 7;8(10):16621-16632
pubmed: 28039470
Am J Hum Genet. 2011 Apr 8;88(4):450-7
pubmed: 21457905
Nature. 2007 May 24;447(7143):433-40
pubmed: 17522677
Genom Data. 2016 May 26;9:22-4
pubmed: 27330998
Hum Mol Genet. 2017 Aug 1;26(15):3014-3027
pubmed: 28854564
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
J Biol Chem. 1994 May 6;269(18):13092-9
pubmed: 8175734
Epigenomics. 2018 Jul;10(7):925-940
pubmed: 29693419
PLoS One. 2013 Jul 10;8(7):e68132
pubmed: 23874521
Hum Mol Genet. 2013 Dec 1;22(23):4726-38
pubmed: 23842454
Respir Res. 2018 Nov 3;19(1):212
pubmed: 30390659