High-throughput DNA analysis shows the importance of methylation in the control of immune inflammatory gene transcription in chronic periodontitis.
High-throughput DNA analysis shows the importance of methylation in the control of immune inflammatory gene transcription in chronic periodontitis.
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DOI：
10.1186/1868-7083-6-15
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发表时间：
2014
影响因子：
5.7
通讯作者：
Line SR
中科院分区：
文献类型：
--
作者：
De Souza AP;Planello AC;Marques MR;De Carvalho DD;Line SR
慢性牙周炎是一种复杂的疾病，难以控制，并没有完全了解。过去的研究证据表明，DNA甲基化在牙周炎的发病机制中起着关键作用。然而，所有的报告都应用了低通量研究基因的技术。为了提高对疾病的认识，我们使用高通量测定分析了与基因转录相关的DNA甲基化变异。Infinium®HumanMethylation450 （Illumina）对12名牙周炎患者和11名年龄匹配的健康个体的牙龈样本进行了检测。从基因本体（Gene Ontology， GO）中提取1284个免疫相关基因和1038个细胞周期相关基因的甲基化数据，从稳定表达基因（在不同生理状态和组织中表达一致的基因）数据集中提取575个基因的甲基化数据，并使用生物信息学工具进行分析。分析了转录起始位点（TSS）的DNA甲基化变化范围为- 2,000至+2,000 bp，并根据健康和牙周炎牙龈组织之间的差异表达微阵列数据集对结果进行了测试。使用来自R统计项目的测试评估差异。牙周炎和正常牙龈组织探针的比较显示，与免疫过程相关的基因的平均甲基化评分和甲基化探针的频率显著降低。在免疫组，这些参数与基因表达呈负相关（Mann-Whitney检验，p < 2.2e−16）。我们的研究结果表明，健康和牙周炎病例之间DNA甲基化的差异在与免疫炎症过程相关的基因中更高。因此，DNA甲基化必须调节染色质区域，从而调节与牙周炎相关的免疫炎症基因的mRNA转录，影响疾病的预后。
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. 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). 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.
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影响因子：
5.3
作者：
Pussinen, Pirkko J.;Alfthan, Georg;Tuomilehto, Jaakko
通讯作者：
Tuomilehto, Jaakko
影响因子：
4.3
作者：
Demmer RT;Behle JH;Wolf DL;Handfield M;Kebschull M;Celenti R;Pavlidis P;Papapanou PN
通讯作者：
Papapanou PN
影响因子：
7.6
作者：
Schaefer, A. S.;Richter, G. M.;Schreiber, S.
通讯作者：
Schreiber, S.
影响因子：
8.3
作者：
Pussinen, PJ;Alfthan, G;Knekt, P
通讯作者：
Knekt, P
DOI：
10.1097/00149831-200410000-00008
发表时间：
2004-10-01
影响因子：
--
作者：
Pussinen, PJ;Alfthan, G;Jousilahti, P
通讯作者：
Jousilahti, P