Epigenetic findings in periodontitis in UK twins: a cross-sectional study
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...
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doaj-aad7b42cbcff41abb20858b6f7982f9d2020-11-24T21:40:45ZengBMCClinical Epigenetics1868-70751868-70832019-02-0111111310.1186/s13148-019-0614-4Epigenetic findings in periodontitis in UK twins: a cross-sectional studyYuko Kurushima0Pei-Chien Tsai1Juan Castillo-Fernandez2Alexessander Couto Alves3Julia Sarah El-Sayed Moustafa4Caroline Le Roy5Tim D. Spector6Mark Ide7Francis J. Hughes8Kerrin S. Small9Claire J. Steves10Jordana T. Bell11Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College LondonUnit of Periodontology, Dental Institute, King’s College LondonUnit of Periodontology, Dental Institute, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College LondonAbstract 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 for 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 tissue 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 at 28 genomic regions was carried out testing for phenotype-methylation associations in 41 (tooth mobility) and 43 (gingival bleeding) buccal, 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 (247 CpG-sites) for chronic periodontitis showed an 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 adult female 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.http://link.springer.com/article/10.1186/s13148-019-0614-4EpigeneticsPeriodontitisDNA methylationGene expressionMetabolomicsEpigenome-wide association scan (EWAS) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuko Kurushima Pei-Chien Tsai Juan Castillo-Fernandez Alexessander Couto Alves Julia Sarah El-Sayed Moustafa Caroline Le Roy Tim D. Spector Mark Ide Francis J. Hughes Kerrin S. Small Claire J. Steves Jordana T. Bell |
spellingShingle |
Yuko Kurushima Pei-Chien Tsai Juan Castillo-Fernandez Alexessander Couto Alves Julia Sarah El-Sayed Moustafa Caroline Le Roy Tim D. Spector Mark Ide Francis J. Hughes Kerrin S. Small Claire J. Steves Jordana T. Bell Epigenetic findings in periodontitis in UK twins: a cross-sectional study Clinical Epigenetics Epigenetics Periodontitis DNA methylation Gene expression Metabolomics Epigenome-wide association scan (EWAS) |
author_facet |
Yuko Kurushima Pei-Chien Tsai Juan Castillo-Fernandez Alexessander Couto Alves Julia Sarah El-Sayed Moustafa Caroline Le Roy Tim D. Spector Mark Ide Francis J. Hughes Kerrin S. Small Claire J. Steves Jordana T. Bell |
author_sort |
Yuko Kurushima |
title |
Epigenetic findings in periodontitis in UK twins: a cross-sectional study |
title_short |
Epigenetic findings in periodontitis in UK twins: a cross-sectional study |
title_full |
Epigenetic findings in periodontitis in UK twins: a cross-sectional study |
title_fullStr |
Epigenetic findings in periodontitis in UK twins: a cross-sectional study |
title_full_unstemmed |
Epigenetic findings in periodontitis in UK twins: a cross-sectional study |
title_sort |
epigenetic findings in periodontitis in uk twins: a cross-sectional study |
publisher |
BMC |
series |
Clinical Epigenetics |
issn |
1868-7075 1868-7083 |
publishDate |
2019-02-01 |
description |
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 for 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 tissue 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 at 28 genomic regions was carried out testing for phenotype-methylation associations in 41 (tooth mobility) and 43 (gingival bleeding) buccal, 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 (247 CpG-sites) for chronic periodontitis showed an 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 adult female 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. |
topic |
Epigenetics Periodontitis DNA methylation Gene expression Metabolomics Epigenome-wide association scan (EWAS) |
url |
http://link.springer.com/article/10.1186/s13148-019-0614-4 |
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