Transcriptomics and methylomics in chronic periodontitis with tobacco use: a pilot study

Clinical Epigenetics, Aug 2017

Background Accumulating evidence suggests that tobacco smoking affects the susceptibility to and severity of chronic periodontitis. Epigenetics may explain the role of smoking in the development and progress of periodontal disease. In this study, we performed transcriptomic and methylomic analyses of non-periodontitis and periodontitis-affected gingival tissues according to smoking status. Methods Human gingival tissues were obtained from 20 patients, including non-smokers with and without periodontitis (n = 5 per group) and smokers with and without periodontitis (n = 5 per group). Total RNA and genomic DNA were isolated, and their quality was validated according to strict standards. The Illumina NextSeq500 sequencing system was used to generate transcriptome and methylome datasets. Results Comprehensive analysis, including between-group correlation, differential gene expression, DNA methylation, gene set enrichment, and protein-protein interaction, indicated that smoking may change the transcription and methylation states of extracellular matrix (ECM) organization-related genes, which exacerbated the periodontal condition. Conclusions Our results suggest that smoking-related changes in DNA methylation patterns and subsequent alterations in the expression of genes coding for ECM components may be causally related to the increased susceptibility to periodontitis in smokers as they could influence ECM organization, which in turn may have an effect on disease characteristics.

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Transcriptomics and methylomics in chronic periodontitis with tobacco use: a pilot study

Cho et al. Clinical Epigenetics Transcriptomics and methylomics in chronic periodontitis with tobacco use: a pilot study Young-Dan Cho 0 1 3 Pil-Jong Kim 0 2 Hong-Gee Kim 2 Yang-Jo Seol 3 Yong-Moo Lee 3 Young Ku 3 In-Chul Rhyu 3 Hyun-Mo Ryoo 1 0 Equal contributors 1 Department of Molecular Genetics, School of Dentistry, Seoul National University , 1 Gwanak-ro, Gwanak-gu, Seoul 08826 , South Korea 2 Department of Dental Services Management and Informatics, School of Dentistry, Seoul National University , 1 Gwanak-ro, Gwanak-gu, Seoul 08826 , South Korea 3 Department of Periodontology, School of Dentistry, Seoul National University , 101 Daehak-no, Jongno-gu, Seoul 03080 , South Korea Background: Accumulating evidence suggests that tobacco smoking affects the susceptibility to and severity of chronic periodontitis. Epigenetics may explain the role of smoking in the development and progress of periodontal disease. In this study, we performed transcriptomic and methylomic analyses of non-periodontitis and periodontitis-affected gingival tissues according to smoking status. Methods: Human gingival tissues were obtained from 20 patients, including non-smokers with and without periodontitis (n = 5 per group) and smokers with and without periodontitis (n = 5 per group). Total RNA and genomic DNA were isolated, and their quality was validated according to strict standards. The Illumina NextSeq500 sequencing system was used to generate transcriptome and methylome datasets. Results: Comprehensive analysis, including between-group correlation, differential gene expression, DNA methylation, gene set enrichment, and protein-protein interaction, indicated that smoking may change the transcription and methylation states of extracellular matrix (ECM) organization-related genes, which exacerbated the periodontal condition. Conclusions: Our results suggest that smoking-related changes in DNA methylation patterns and subsequent alterations in the expression of genes coding for ECM components may be causally related to the increased susceptibility to periodontitis in smokers as they could influence ECM organization, which in turn may have an effect on disease characteristics. DNA methylation; Epigenomics; Extracellular matrix; Periodontal disease; Smoking; Transcriptome Background Periodontal diseases are typical inflammatory conditions caused by bacterial infection and promoted by environmental factors or other modifying factors [ 1 ]. Chronic periodontitis presents a destructive periodontal disease that leads to alveolar bone resorption [ 2 ]. Tobacco smoking is considered a major risk factor, and many studies have demonstrated that smoking alters the development and progression of periodontitis [ 3–5 ]. Other risk factors that modify the host response to the challenge of bacterial infection and may induce periodontitis are alcohol, diet, pollution, and drugs [ 6 ]. An increasing number of recent studies have focused on the role of epigenetic events in the development of various diseases [ 7, 8 ]. Unlike genetics which analyzes changes in the DNA sequence, epigenetics represents the study of cellular or physiological phenotypic trait variations caused by environmental or external factors, which modulate gene expression without altering DNA sequence [9]. Epigenetic modifications include chemical alteration of DNA and associated proteins such as histones, which leads to chromatin remodeling and plays an important role in regulating gene expression [ 10 ]. Among these effects, DNA methylation is a common epigenetic mechanism observed in human cells [ 11 ]. DNA methylation carried out by DNA methyltransferases typically occurs in CpG dinucleotide-rich regions termed “CpG islands,” which are mainly located in gene promoters, and is associated with gene silencing [ 12 ]. The methylated sites interact with the methyl-CpGbinding domain proteins (MBDs) which in turn recruit histone deacetylase-containing complexes and induce histone condensation. Moreover, histones can also be directly modified by methylation. Both mechanisms block the binding of transcription factors to gene loci; however, while histone modification is transient, DNA methylation exhibits a more stable nature of gene regulation [ 13 ]. Some reports have suggested that the CpG methylation status of inflammation-related genes (e.g., IL-2 and IL-8) is implicated in gene expression in chronic periodontitis [ 12, 14, 15 ]. Most epigenetic studies of periodontitis used low-throughput-level screening and were focused on host response to bacterial infection [ 16, 17 ], while the impact of environmental or external factors on DNA methylation was somewhat neglected. The aim of this study was to test a hypothesis that tobacco smoking could change the epigenetic state of periodontal cells and modulate the susceptibility to or severity of periodontitis. To determine whether this is the case, we performed comprehensive genome-wide high-throughput analy (...truncated)


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Young-Dan Cho, Pil-Jong Kim, Hong-Gee Kim, Yang-Jo Seol, Yong-Moo Lee, Young Ku, In-Chul Rhyu, Hyun-Mo Ryoo. Transcriptomics and methylomics in chronic periodontitis with tobacco use: a pilot study, Clinical Epigenetics, 2017, pp. 81, Volume 9, Issue 1, DOI: 10.1186/s13148-017-0381-z