Wawrzyniak Marcin, Scharl Michael
Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Switzerland.
Swiss Med Wkly. 2018 Sep 23;148:w14671. doi: 10.4414/smw.2018.14671. eCollection 2018 Sep 10.
The relevance of genetic and epigenetic alterations in the pathogenesis of inflammatory bowel disease (IBD) is still poorly understood. So far, 240 risk gene loci have been associated with IBD. They are mainly involved in regulating innate and adaptive immunity, as well as maintaining intestinal epithelial barrier function. However, the functional consequences of the identified genetic polymorphisms for IBD pathogenesis in vivo are often unknown. Even less is known about the role for epigenetic modifications in IBD pathogenesis. Though a number of epigenetic events seem to be causatively involved IBD pathogenesis, our knowledge about the functional relevance of those epigenetic modifications is scanty. This opens up a broad research field that generates novel insights into the pathophysiology of intestinal and chronic inflammatory disease. Patterns of DNA methylation and histone modifications might serve not only as biomarkers of disease activity or disease course, but also as new targets in therapeutic interventions in IBD patients.
遗传和表观遗传改变在炎症性肠病（IBD）发病机制中的相关性仍未得到充分理解。到目前为止，已有240个风险基因位点与IBD相关联。它们主要参与调节先天性和适应性免疫，以及维持肠道上皮屏障功能。然而，体内已鉴定出的基因多态性对IBD发病机制的功能影响往往尚不清楚。关于表观遗传修饰在IBD发病机制中的作用了解得更少。尽管一些表观遗传事件似乎与IBD发病机制有因果关系，但我们对这些表观遗传修饰的功能相关性的了解却很少。这开辟了一个广阔的研究领域，能为肠道和慢性炎症性疾病的病理生理学带来新的见解。DNA甲基化和组蛋白修饰模式不仅可能作为疾病活动或病程的生物标志物，还可能成为IBD患者治疗干预的新靶点。
