Table 1 Overview of epigenetic studies in periodontology
Specific gene | |||
|---|---|---|---|
Publication | Methods | Targets | Results |
(1) DNA methylation | |||
Oliveira et al. [107] | Methylation Specific PCR (MSP) | Interleukin (IL)-8 | Individuals with chronic periodontitis, independent of smoking habit, have a higher percentage of hypomethylation of the IL-8 gene |
Andia et al. [108] | MSP | IL-8 | A marked hypomethylated status in the promoter region of the IL-8 gene was found in aggressive periodontitis |
Loo et al. [109] | MSP | E-cadherin, COX-2 | The methylation of CpG islands in E-Cadherin and COX-2 genes in periodontitis patients occurs more frequently in periodontitis patients |
Zhang et al. [110] | Pyrosequencing | (Interferon)IFN-γ | A hypomethylation profile within IFNG promoter region is related to an increase of IFNG transcription present in the chronic periodontitis |
Zhang et al., 2010 [111] | Bisulfite-specific PCR (BSP) | Prostaglandin-endoperoxide synthase (PTGS)2 | The increase of methylation in chronic periodontitis was associated with a level of PTGS2 mRNA expression |
de Oliveria et al. [112] | Methylation-Sensitive Restriction Enzyme-PCR (MSRE-PCR) | Toll-like receptor (TLR)2, TLR4 | No significant differences on DNA methylation status of the TRL2 and TRL4 gene promoters in periodontitis |
Viana et al. [113] | MSP, BSP | IFN-γ, IL-10 | No significant differences on DNA methylation status of the IFN-γ and IL-10 genes were observed |
Ishida et al. [114] | BSP | IL-6 | Hypomethylated status of a single CpG in the IL‐6 promoter region may lead to increased levels of serum IL‐6, implicating a role in the pathogenesis of chronic periodontitis |
de Faria Amormino et al. [115] | MSRE-PCR | TLR2 | Positive correlation between the TLR2 methylation frequency and probing depth was observed in periodontitis |
Stefani et al. [116] | MSP | IL-6 | The high expression of IL-6 is an important factor related to chronic periodontitis, but was not associated with methylation status |
Zhang et al. [117] | BSP, Pyrosequencing | Tumor necrosis factor (TNF)-α | Increased methylation of TNF-α in chronic periodontitis compared to those with gingival health |
Baptista et al. [88] | COmbined Bisulfite Restriction Analysis (COBRA) | suppressors of cytokine signaling (SOCS)-1, long interspersed nuclear element (LINE)-1 | Different DNA methylation status of SOCS1 and LINE-1 was observed in infected oral environment |
Andia et al. [89] | MSRE-PCR | SOCS-1,3 and LINE-1 | DNA methylation levels for SOCS1 and SOCS3 did not differ between healthy and periodontitis groups |
Kobayasi et al. [118] | BSP | IL-6 | The increased expression of IL-6 gene may be related to IL-6 promoter hypomethylation in periodontitis |
Kojima et al. [119] | BSP | TNF-α | The hypermethylated status of CpG motifs in the TNF-α gene promoter in blood cells may be unique to Japanese adults with chronic periodontitis |
Schulz et al. [120] | PCR array | 22 inflammatory candidate genes including CCL25 and IL17C | Differential methylation pattern for CCL25 and IL17C in periodontitis was observed |
Asa'ad et al. [121] | Pyrosequencing | LINE-1, COX-2, IFN-γ, TNF-α | Periodontal therapy did not influence gene expression methylation of TNF‐α, IFN‐γ and LINE‐1 levels; however, it significantly reduced COX‐2 methylation levels |
Shaddox [122] | Pyrosequencing | TLR signaling genes (FADD,MAP3K7,MYD88,IL6R,PPARA,IRAK1BP1,RIPK2) | Significant differences in methylation between LAP patients compared to healthy controls were observed |
Li et al. [123] | Pyrosequencing | MMP-9 and TIMP-1 | Positive correlation between methylation levels of MMP-9 CpG islands and the severity of chronic periodontitis was found |
Genome-wide | ||
|---|---|---|
Publications | Methods | Results |
Barros et al. [4] | CpG methylation array | The methylation status of some of these CpG regions suggests linkages with inflammatory pathways associated with acute and chronic inflammatory states |
De Souza et al. [124] | Genome-wide methylation assay | Variations in DNA methylation between healthy and periodontitis cases are higher in genes related to the immune-inflammatory process |
Cho et al. [39] | RNA sequencing, Reduced representation bisulfite sequencing (RRBS) | Smoking may change the transcription and methylation states of extracellular matrix (ECM) organization-related genes, which exacerbated the periodontal condition |
Cho et al. [87] | RNA sequencing, RRBS | Periodontitis and peri-implantitis share biological similarities; however, hierarchical clustering between the two disease groups revealed distinct molecular characteristics |
Publications | Methods | Target | Results |
|---|---|---|---|
(2) Histone modification | |||
Cantley et al. [90] | Histone deacetylase inhibitor (HDACi) treatment to mouse model of periodontitis | Histone deacetylase | HDACi effectively suppresses bone loss in the mouse model of periodontitis |
Larsson et al. [125] | Chromatin immunoprecipitation (ChIP) assay | IL-10 | LPS stimulation of B cells resulted in an increase in acetylation of H4 and methylation of H3 |
Martins et al. [85] | Immunohistochemistry about histone modification in mouse periodontitis model | Acetylation in H3K9 | Toll-like receptors 1, 2, and 4 and the nucleotide-binding oligomerization domain protein 1 induced histone acetylation in oral epithelial cells |
Publications | Methods | Target | Results |
|---|---|---|---|
(3) Long non-coding RNAs (lncRNAs) | |||
Gholami et al. [126] | Real-time PCR | ANRIL lncRNA | Expression of ANRIL was significantly lower in the blood of periodontitis |
Li et al. [95] | Real time PCR | MALAT1 lncRNA | MALAT1 up-regulated in the gingival tissue of chronic periodontitis MALAT1 enhances inflammatory cytokine production via miR-20A and releasing TLR4 |
Wang et al. [94] | Real-time PCR | POIR lncRNA | POIR lncRNA may act as a competing endogenous RNA for miR-182, leading to derepression of target gene, FoxO1 |