Abnormal DNA methylation has been described in human inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD). As other complex diseases, IBD results from the balance between genetic predisposition and environmental exposures. As such, DNA methylation may be the consequence (and potential effector) of both, genetic susceptibility variants and/or environmental signals such as cytokine exposure. We attempted to discern between these two non-excluding possibilities by performing a combined analysis of published DNA methylation data in intestinal mucosal cells of IBD and control samples. We identified abnormal DNA methylation at different levels: deviation from mean methylation signals at site and region levels, and differential variability. A fraction of such changes is associated with genetic polymorphisms linked to IBD susceptibility. In addition, by comparing with another intestinal inflammatory condition (i.e., coeliac disease) we propose that aberrant DNA methylation can also be the result of unspecific processes such as chronic inflammation. Our characterization suggests that IBD methylomes combine intrinsic and extrinsic responses in intestinal mucosal cells, and could point to knowledge-based biomarkers of IBD detection and progression.

DNA甲基化异常已在胃肠道的人类炎性疾病（如炎性肠病（IBD））中描述。与其他复杂疾病一样，IBD是由遗传易感性和环境暴露之间的平衡引起的。因此，DNA甲基化可能是遗传敏感性变异和/或环境信号（例如细胞因子暴露）的结果（和潜在的效应物）。我们试图通过对IBD和对照样品的肠粘膜细胞中已发表的DNA甲基化数据进行组合分析，来辨别这两种不可排除的可能性。我们在不同的水平上鉴定出异常的DNA甲基化：在位点和区域水平上偏离平均甲基化信号，以及差异性。这种变化的一小部分与与IBD易感性有关的遗传多态性有关。此外，通过与另一种肠道炎症性疾病（即乳糜泻）进行比较，我们提出异常的DNA甲基化也可能是非特异性过程（例如慢性炎症）的结果。我们的特征表明，IBD甲基化组结合了肠道粘膜细胞的内在和外在反应，并且可能指向IBD检测和进展的基于知识的生物标记。