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Epigenetic findings in periodontitis in UK twins: a cross sectional study

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Original languageEnglish
Article number27
JournalClinical Epigenetics
Volume11
Issue number1
Publication statusPublished - 13 Feb 2019

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Abstract

Background: Genetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease. Methods: Self-reported gingival bleeding, and history of gum disease or tooth mobility were used as indicators of periodontal disease. DNA methylation profiles were generated using the Infinium HumanMethylation450 BeadChip in whole blood, buccal, and adipose samples from predominantly older female twins (mean age 58) from the TwinsUK cohort. Epigenome-wide association scans (EWAS) of gingival bleeding and tooth mobility were conducted in whole blood in 528 and 492 twins, respectively. Subsequently, targeted candidate gene analysis including 28 genomic signals was performed for phenotype-methylation associations in 41 (Tooth mobility) and 43 (Gingival bleeding) buccal samples, and 501 (Tooth mobility) and 556 (Gingival bleeding) adipose DNA samples. Results: Epigenome-wide analyses in blood identified one CpG-site (cg21245277 in ZNF804A) associated with gingival bleeding (FDR=0.03, nominal p-value=7.17e-8), and 58 sites associated with tooth mobility (FDR<0.05) with the top signals in IQCE and XKR6. Epigenetic variation at 28 candidate regions (256 CpG-sites) for chronic periodontitis showed a strong enrichment for association with periodontal traits, and signals in eight genes (VDR, IL6ST, TMCO6, IL1RN, CD44, IL1B, WHAMM, and CXCL1) were significant in both traits. The methylation-phenotype association signals validated in buccal samples, and a subset (25%) also validated in adipose tissue. Conclusions: Epigenome-wide analyses in female adult twins identified specific DNA methylation changes linked to self-reported periodontal disease. Future work will explore the environmental basis and functional impact of these results to infer potential for strategic personalized treatments and prevention of chronic periodontitis.

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