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Background <p>Methylation of DNA is an epigenetic reversible process that regulates gene expression. Aberrant promoter methylation is associated with chronic inflammation; however, the genome-wide DNA promoter methylation signature in periodontitis remains unexplored.</p> Methods <p>The present study is an epigenome-wide association study (EWAS) aimed at investigating salivary DNA methylation patterns within gene promoter regions in individuals with Stage III/IV periodontitis compared to healthy controls. Cases (all available individuals with Stage III/IV and probing pocket depths (PPD) &gt; 5&#xa0;mm, <i>n</i> = 50, 48% women) were participants in an oral health examination (40–54-year-old subsample, <i>n</i> = 1668) of the population-based seventh survey of the Tromsø Study, conducted from 2015 to 2016. Periodontally healthy controls with similar age and sex to the cases (<i>n</i> = 50, 58% women) were randomly selected from the same subsample. We used the Illumina DNA methylation BeadChip technology, targeting ~ 935&#xa0;K unique methylation sites. The R package RnBeads was used to study the difference in methylation. Separate lists of all significantly (comb.p.adj.fdr &lt; 0.05) hypomethylated (hypoMPs, <i>n</i> = 3411) and hypermethylated (hyperMPs, <i>n</i> = 3437) promoters in participants with periodontitis relative to controls were used as inputs for enrichment analysis (g:Profiler) and network visualization (Cystoscape).</p> Results <p>Gene ontology terms enriched among the hypoMPs included DNA biosynthesis, cell cycle/checkpoint, nuclear chromosome, endoplasmic reticulum, regulation of inflammatory response and leucocyte activation, cell adhesion, TRIF-dependent Toll-like receptor signaling, tyrosine phosphorylation of STAT proteins, regulation of PI3K/Akt, collagen extracellular matrix, and mucopolysaccharide metabolic process. HyperMPs were enriched in mRNA catabolism, mitochondrial electron transport, intrinsic apoptotic signaling, B-lymphocyte differentiation, actin cytoskeleton, regulation of extracellular matrix organization, epithelial-mesenchymal transition, ubiquitination, wound healing, acylglycerol metabolism, and serine/threonine signaling. NF-κB, GMEB-1, and IRF-8 were enriched in hypoMPs; ZFP85, ELF-5, and HNF4-alpha in hyperMPs.</p> Conclusions <p>We identified a differential DNA promoter methylation signature in participants with Stage III/IV periodontitis in middle adulthood. Our study highlights biological pathways involved in inflammation, immune response, tissue destruction, and repair that may be epigenetically dysregulated.</p>

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Genome-wide profiling of salivary promoter-region DNA methylation in periodontitis: the Tromsø Study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月7日

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  • Natalia Petrenya,
  • Birgitta Jönsson,
  • Elin Hadler-Olsen,
  • Lena Larsson,
  • Arnar Flatberg,
  • Vidar Beisvåg,
  • Gro Eirin Holde,
  • Svetlana N. Zykova,
  • Farah Asa’ad

摘要

Background

Methylation of DNA is an epigenetic reversible process that regulates gene expression. Aberrant promoter methylation is associated with chronic inflammation; however, the genome-wide DNA promoter methylation signature in periodontitis remains unexplored.

Methods

The present study is an epigenome-wide association study (EWAS) aimed at investigating salivary DNA methylation patterns within gene promoter regions in individuals with Stage III/IV periodontitis compared to healthy controls. Cases (all available individuals with Stage III/IV and probing pocket depths (PPD) > 5 mm, n = 50, 48% women) were participants in an oral health examination (40–54-year-old subsample, n = 1668) of the population-based seventh survey of the Tromsø Study, conducted from 2015 to 2016. Periodontally healthy controls with similar age and sex to the cases (n = 50, 58% women) were randomly selected from the same subsample. We used the Illumina DNA methylation BeadChip technology, targeting ~ 935 K unique methylation sites. The R package RnBeads was used to study the difference in methylation. Separate lists of all significantly (comb.p.adj.fdr < 0.05) hypomethylated (hypoMPs, n = 3411) and hypermethylated (hyperMPs, n = 3437) promoters in participants with periodontitis relative to controls were used as inputs for enrichment analysis (g:Profiler) and network visualization (Cystoscape).

Results

Gene ontology terms enriched among the hypoMPs included DNA biosynthesis, cell cycle/checkpoint, nuclear chromosome, endoplasmic reticulum, regulation of inflammatory response and leucocyte activation, cell adhesion, TRIF-dependent Toll-like receptor signaling, tyrosine phosphorylation of STAT proteins, regulation of PI3K/Akt, collagen extracellular matrix, and mucopolysaccharide metabolic process. HyperMPs were enriched in mRNA catabolism, mitochondrial electron transport, intrinsic apoptotic signaling, B-lymphocyte differentiation, actin cytoskeleton, regulation of extracellular matrix organization, epithelial-mesenchymal transition, ubiquitination, wound healing, acylglycerol metabolism, and serine/threonine signaling. NF-κB, GMEB-1, and IRF-8 were enriched in hypoMPs; ZFP85, ELF-5, and HNF4-alpha in hyperMPs.

Conclusions

We identified a differential DNA promoter methylation signature in participants with Stage III/IV periodontitis in middle adulthood. Our study highlights biological pathways involved in inflammation, immune response, tissue destruction, and repair that may be epigenetically dysregulated.