High-throughput DNA analysis shows the importance of methylation in the control of immune inflammatory gene transcription in chronic periodontitisReport as inadecuate




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Clinical Epigenetics

, 6:15

First Online: 12 August 2014Received: 14 May 2014Accepted: 24 July 2014

Abstract

BackgroundChronic periodontitis represents a complex disease that is hard to control and is not completely understood. Evidence from past studies suggests that there is a key role for DNA methylation in the pathogenesis of periodontitis. However, all reports have applied technologies that investigate genes in a low throughput. In order to advance in the knowledge of the disease, we analyzed DNA methylation variations associated with gene transcription using a high-throughput assay. Infinium® HumanMethylation450 Illumina was performed on gingival samples from 12 periodontitis cases and 11 age-matched healthy individuals. Methylation data of 1,284 immune-related genes and 1,038 cell cycle-related genes from Gene Ontology GO and 575 genes from a dataset of stably expressed genes genes with consistent expression in different physiological states and tissues were extracted from a microarray dataset and analyzed using bioinformatics tools. DNA methylation variations ranging from −2,000 to +2,000 bp from the transcription start site TSS were analyzed, and the results were tested against a differential expression microarray dataset between healthy and periodontitis gingival tissues. Differences were evaluated using tests from the R Statistical Project.

ResultsThe comparison of probes between periodontitis and normal gingival tissues showed that the mean methylation scores and the frequency of methylated probes were significantly lower in genes related to the immune process. In the immune group, these parameters were negatively correlated with gene expression Mann-Whitney test, p < 2.2e − 16.

ConclusionsOur results show that variations in DNA methylation between healthy and periodontitis cases are higher in genes related to the immune-inflammatory process. Thus, DNA methylation must be modulating chromatin regions and, consequently, modulating the mRNA transcription of immune-inflammatory genes related with periodontitis, impacting the prognosis of disease.

KeywordsChronic periodontitis DNA methylation Epigenetics Inflammation Transcription Electronic supplementary materialThe online version of this article doi:10.1186-1868-7083-6-15 contains supplementary material, which is available to authorized users.

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