Identification of disease-associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease
Identification of disease-associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease
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DOI：
10.1111/j.1399-0004.2010.01546.x
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发表时间：
2011-07-01
影响因子：
3.5
通讯作者：
Koltun, W. A.
中科院分区：
文献类型：
--
作者：
Lin, Z.;Hegarty, J. P.;Koltun, W. A.
压倒性的证据支持炎症性肠病（IBD）是由多个基因的遗传易感性之间复杂的相互作用，加上与环境因素的异常相互作用引起的理论。越来越明显的是，表观遗传因素可以在疾病的发病机制中起重要作用。IBD相关基因甲基化状态的变化可能显著改变基因表达水平，可能导致疾病的发生和进展。我们探讨了DNA甲基化在IBD发病机制中的作用。使用GoldenGate（TM）甲基化分析对来自26名IBD患者[克罗恩病（CD）n = 9，溃疡性结肠炎（UC）n = 17]的匹配的患病（n = 26）和非患病（n = 26）肠组织的DNA甲基化谱（807个基因的1505个CpG位点）进行分析。在从训练组（14个非患病组织和14个患病组织）中初步鉴定了一组50个差异甲基化的CpG位点并随后用测试组（12个非患病组织和12个患病组织）进行验证后，我们鉴定了IBD患者肠组织中差异甲基化的7个CpG位点。我们还鉴定了与两种主要IBD亚型CD和UC相关的DNA甲基化变化。这项研究报告了IBD相关的肠道组织DNA甲基化变化，这可能是疾病亚型特异性的。
Overwhelming evidence supports the theory that inflammatory bowel disease (IBD) is caused by a complex interplay between genetic predispositions of multiple genes, combined with an abnormal interaction with environmental factors. It is becoming apparent that epigenetic factors can have a significant contribution in the pathogenesis of disease. Changes in the methylation state of IBD-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We have explored the role of DNA methylation in IBD pathogenesis. DNA methylation profiles (1505 CpG sites of 807 genes) of matched diseased (n = 26) and non-diseased (n = 26) intestinal tissues from 26 patients with IBD [Crohn's disease (CD) n = 9, ulcerative colitis (UC) n = 17] were profiled using the GoldenGate (TM) methylation assay. After an initial identification of a panel of 50 differentially methylated CpG sites from a training set (14 non-diseased and 14 diseased tissues) and subsequent validation with a testing set (12 non-diseased and 12 diseased tissues), we identified seven CpG sites that are differentially methylated in intestinal tissues of IBD patients. We have also identified changes in DNA methylation associated with the two major IBD subtypes, CD and UC. This study reports IBD-associated changes in DNA methylation in intestinal tissue, which may be disease subtype-specific.