Journal
JOURNAL OF CLINICAL PERIODONTOLOGY
Volume 48, Issue 9, Pages 1152-1164Publisher
WILEY
DOI: 10.1111/jcpe.13504
Keywords
epigenetics; gingivitis; pathogenesis; periodontitis; transcriptomics
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Funding
- NIH/NIDCR [DE015649, DE021820, DE024735]
- National Center for Advancing Translational Sciences [TR000040]
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The study investigated differential DNA methylation in gingival tissues in periodontal health, gingivitis, and periodontitis, and its association with differential mRNA expression. The concomitant study of DNA methylation and gene expression patterns may identify genes whose expression is epigenetically regulated in periodontitis.
Aim We investigated differential DNA methylation in gingival tissues in periodontal health, gingivitis, and periodontitis, and its association with differential mRNA expression. Materials and methods Gingival tissues were harvested from individuals and sites with clinically healthy and intact periodontium, gingivitis, and periodontitis. Samples were processed for differential DNA methylation and mRNA expression using the IlluminaEPIC (850 K) and the IlluminaHiSeq2000 platforms, respectively. Across the three phenotypes, we identified differentially methylated CpG sites and regions, differentially expressed genes (DEGs), and genes with concomitant differential methylation at their promoters and expression were identified. The findings were validated using our earlier databases using HG-U133Plus2.0Affymetrix microarrays and Illumina (450 K) methylation arrays. Results We observed 43,631 differentially methylated positions (DMPs) between periodontitis and health, and 536 DMPs between gingivitis and health (FDR < 0.05). On the mRNA level, statistically significant DEGs were observed only between periodontitis and health (n = 126). Twelve DEGs between periodontitis and health (DCC, KCNA3, KCNA2, RIMS2, HOXB7, PNOC, IRX1, JSRP1, TBX1, OPCML, CECR1, SCN4B) were also differentially methylated between the two phenotypes. Spearman correlations between methylation and expression in the EPIC/mRNAseq dataset were largely replicated in the 450 K/Affymetrix datasets. Conclusions Concomitant study of DNA methylation and gene expression patterns may identify genes whose expression is epigenetically regulated in periodontitis.
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