Van Limbergen Johan, Russell Richard K, Nimmo Elaine R, Satsangi Jack
Gastrointestinal Unit, Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom.
Am J Gastroenterol. 2007 Dec;102(12):2820-31. doi: 10.1111/j.1572-0241.2007.01527.x. Epub 2007 Sep 25.
Great progress in the understanding of the molecular genetics of inflammatory bowel disease (IBD) has been made over the last 10 years. Strong epidemiological evidence, based initially on concordance data in twin/family studies, led to the application of genome-wide linkage analysis involving multiply affected families and the identification of a number of susceptibility loci. Further characterization of the IBD1 locus on chromosome 16 led to the discovery of the NOD2/CARD15 gene as the first susceptibility gene in Crohn's disease for 2001. This landmark finding has led to a redirection of basic research in IBD with interest focused principally on regulation of the innate immune response and mucosal barrier function. Within the last year, the use of genome-wide association studies has provided new insights into primary pathogenetic mechanisms; several new genes such as the Interleukin-23 receptor (IL23R) and ATG16L1 (autophagy-related 16-like 1) genes are strongly implicated. Overall, these studies promise to change our fundamental understanding of IBD pathophysiology and to have implications for clinical practice.
在过去十年中，我们对炎症性肠病（IBD）分子遗传学的理解取得了巨大进展。最初基于双胞胎/家族研究中的一致性数据的强有力的流行病学证据，促使人们对多个患病家族进行全基因组连锁分析，并确定了一些易感基因座。对16号染色体上IBD1基因座的进一步表征，导致在2001年发现NOD2/CARD15基因是克罗恩病的首个易感基因。这一具有里程碑意义的发现使得IBD基础研究的方向发生了转变，研究兴趣主要集中在天然免疫反应和黏膜屏障功能的调节上。在过去的一年里，全基因组关联研究的应用为原发性发病机制提供了新的见解；几个新基因，如白细胞介素-23受体（IL23R）和自噬相关16样蛋白1（ATG16L1）基因，被强烈认为与之相关。总体而言，这些研究有望改变我们对IBD病理生理学的基本认识，并对临床实践产生影响。
