Mucosal genome-wide methylation changes in inflammatory bowel disease
Mucosal genome-wide methylation changes in inflammatory bowel disease
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DOI：
10.1002/ibd.22942
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发表时间：
2012-11-01
影响因子：
4.9
通讯作者：
Parkes, Miles
中科院分区：
文献类型：
--
作者：
Cooke, James;Zhang, Hu;Parkes, Miles
背景：DNA甲基化是细胞调控基因转录的关键表观遗传机制。它的作用包括对基因表达的动态调节，例如，作为进化免疫反应的一部分，以及特殊组织中的细胞分化。在这里，我们的目的是研究肠道甲基化模式的差异对炎症性肠病(IBD)易感性和活动性的影响。方法：从直肠活检组织中提取DNA后，我们使用粒芯片芯片进行全基因组甲基化分析，以确定溃疡性结肠炎和克罗恩病患者和健康对照组之间存在差异甲基化的基因。选定的甲基化信号在独立的复制小组中通过焦磷酸测序进行验证。通过实时定量聚合酶链式反应(RT-PCR)寻找与基因表达的相关性。结果：多个基因显示差异甲基化的显著证据，其中几个出现在溃疡性结肠炎和克罗恩病的比较中，包括THRAP2、FANCC、GBGT1、DOK2、TNFSF4、TNFSF12和FUT7。在全基因组关联扫描中，包括CARD9、ICAM3和IL8RB在内的多个基因与先前被认为在IBD易感性中发挥作用的基因偶然重叠(P<；0.001)。在选定的转录本中，甲基化和基因表达之间的相关性被确定。结论：在IBD患者和对照组之间，这些基因调控位点上DNA甲基化的一致差异表明它们的转录改变与IBD的发病有关。(2012年炎症性肠病；)
Background: DNA methylation constitutes a key epigenetic mechanism by which cells regulate gene transcription. Among its roles are the dynamic regulation of gene expression, for example, as part of an evolving immune response, and cell differentiation in specialized tissues. Here our aim was to study the impact of differences in methylation patterns in the intestine with regard to inflammatory bowel disease (IBD) susceptibility and activity. Methods: Having extracted DNA from rectal biopsies, we conducted genome-wide methylation profiling using the HumanMethylation27 BeadChip microarray to identify genes showing evidence of differential methylation between cases of ulcerative colitis and Crohn's disease and healthy controls. Selected methylation signals were validated in an independent replication panel by pyrosequencing. Correlation with gene expression was sought by quantitative real-time polymerase chain reaction (RT-PCR). Results: Multiple genes showed significant evidence of differential methylation, several appearing in both ulcerative colitis and Crohn's disease comparisons including THRAP2, FANCC, GBGT1, DOK2, TNFSF4, TNFSF12, and FUT7. Many more than expected by chance overlapped with genes previously implicated as playing a role in IBD susceptibility in genome-wide association scans, including CARD9, ICAM3, and IL8RB (P < 0.001). Correlation between methylation and gene expression was identified for selected transcripts. Conclusions: Consistent differences in DNA methylation between IBD cases and controls at regulatory sites within these genes suggest that their altered transcription contributes to IBD pathogenesis. (Inflamm Bowel Dis 2012;)