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

Clinical Epigenetics

Sergio Roberto Peres Line²  Daniel Diniz De Carvalho¹  Marcelo Rocha Marques²  Aline Cristiane Planello¹  Ana Paula De Souza² 

[1] Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, ON M5G 2M9, Canada;Department of Morphology, School of Dentistry of Piracicaba, FOP-UNICAMP, University of Campinas, Av. Limeira 901, Piracicaba, SP 13414-018, Brazil

关键词: Transcription;    Inflammation;    Epigenetics;    DNA methylation;    Chronic periodontitis;   

Others  :  1092844
DOI  :  10.1186/1868-7083-6-15

 received in 2014-05-14, accepted in 2014-07-24,  发布年份 2014

【 摘 要 】

Background

Chronic 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.

Results

The 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).

Conclusions

Our 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.

【 授权许可】

   
2014 De Souza et al.; licensee BioMed Central Ltd.

【 图 表 】

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