IBD candidate genes and intestinal barrier regulation.
IBD candidate genes and intestinal barrier regulation.
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DOI：
10.1097/mib.0000000000000090
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发表时间：
2014-10
影响因子：
4.9
通讯作者：
McCole DF
中科院分区：
文献类型：
--
作者：
McCole DF
人类遗传学大规模分析技术的进步，使人们对包括炎症性肠病（IBD）、克罗恩病和溃疡性结肠炎在内的慢性疾病可能的遗传因素有了深刻的认识。到目前为止，已有163个不同的遗传风险位点与克罗恩病或溃疡性结肠炎相关联，且这两种疾病之间存在大量的基因重叠。尽管许多风险变异与疾病呈现出可重复的相关性，但单个基因关联仅影响一部分患者，而且这些风险变异对IBD发病的功能性作用在很大程度上尚未确定。尽管对双胞胎的研究表明，IBD的发生并非仅仅由遗传风险介导，但阐明风险变异对已知调节IBD中受损的关键生理过程的相关细胞类型中基因功能的功能性影响仍然很重要。本文将讨论已知或疑似参与调节肠上皮屏障以及这一动态且多功能的细胞层所主导的若干生理过程的IBD候选基因。这将包括紧密连接的组装和调节、细胞黏附与极性、黏液和糖蛋白调节、细菌感知、膜转运、上皮分化和修复。
Technological advances in the large scale analysis of human genetics have generated profound insights into possible genetic contributions to chronic diseases including the inflammatory bowel diseases (IBDs), Crohn’s disease and ulcerative colitis. To date, 163 distinct genetic risk loci have been associated with either Crohn’s disease or ulcerative colitis, with a substantial degree of genetic overlap between these 2 conditions. Although many risk variants show a reproducible correlation with disease, individual gene associations only affect a subset of patients, and the functional contribution(s) of these risk variants to the onset of IBD is largely undetermined. Although studies in twins have demonstrated that the development of IBD is not mediated solely by genetic risk, it is nevertheless important to elucidate the functional consequences of risk variants for gene function in relevant cell types known to regulate key physiological processes that are compromised in IBD. This article will discuss IBD candidate genes that are known to be, or are suspected of being, involved in regulating the intestinal epithelial barrier and several of the physiological processes presided over by this dynamic and versatile layer of cells. This will include assembly and regulation of tight junctions, cell adhesion and polarity, mucus and glycoprotein regulation, bacterial sensing, membrane transport, epithelial differentiation, and restitution.