Evidence map›Paper›PMID 41818416›Full record

ArticleClinical and experimental dental research2026

Epigenetic Alterations Beyond CpG Islands in Periodontitis: In Silico Study of DNA Methylation Data.

Koki Yoshida, Gowri Sivaramakrishnan, Farah Asa'ad

Abstract read
In one paragraph

Article in Clinical and experimental dental research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Koki YoshidaDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, Japan.
Gowri SivaramakrishnanBahrain Defence Force Royal Medical Services, Riffa, Bahrain.ORCID 0000-0002-5877-205X
Farah Asa'adDepartment of Oral Biochemistry, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0001-5186-2645

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTo classify differentially methylated CpG sites in periodontitis based on methylation shift direction and location relative to CpG islands. MATERIAL AND

methodsWe integrated DNA methylation data from 65 gingival samples (31 periodontitis, 34 healthy) from three GEO datasets. Preprocessing included normalization using R pipelines. Differential DNA methylation analysis was performed with the limma package. CpG sites (adjusted p < 0.05) were further evaluated using an exploratory threshold-crossing framework based on group-mean β-values (cutoff = 0.5) identifying Control low → Periodontitis high and Control high → Periodontitis low shifts, annotated with Illumina 450k references. Top 20 CpG-associated genes were selected by absolute logFC. Gene Ontology (GO) enrichment was conducted using clusterProfiler.

resultsWe identified 164,400 differentially methylated CpG sites, including CpGs exhibiting Control low → Periodontitis high and Control high → Periodontitis low shifts, and mapped to gene features. Nearly half of methylation alterations (47.77%) were in OpenSea regions, with additional signals in CpG islands and promoter-proximal regions. GO enrichment analysis revealed that differentially methylated genes in periodontitis were associated with epithelial and organ morphogenesis, including epithelial tube morphogenesis, epithelial cell proliferation, and cell fate commitment. Enriched cellular components were membrane- and vesicle-associated structures, while molecular functions were transmembrane transporter activity, ion channel activity, and DNA-binding transcription factor-related functions. These findings suggest that DNA methylation alterations in periodontitis are linked to epigenetic regulation of epithelial structure and tissue remodeling, with implications for immune-related cellular processes. Among the top 20 genes exhibiting β-threshold-based directionality changes, 13 were significantly enriched in GO terms: 8 in the Control low → Periodontitis high group (DGKA, CHMP6, RUNX2, CDKL1, SLC6A3, CFTR, HLA-C, LRIG1), 5 in the Control high → Periodontitis low group (AP2A2, PARD3, PADI2, FOXK1, RGS1).

conclusionsThis study provides an exploratory, direction-aware summary framework of DNA methylation in periodontitis, highlighting functional changes beyond CpG islands and identifying candidate genes for further functional validation.

Indexed as

CpG IslandsDNA MethylationEpigenesis, GeneticPeriodontitisComputer SimulationGene OntologyHumansCpG islandsDNA methylationepigeneticsGene Ontology analysismethylation directionalityperiodontitis

Identifiers

PMID41818416
PMCPMC13140714

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.