A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
复制标题
DOI：
10.1038/35079114
复制
发表时间：
2001-05-31
期刊：
影响因子：
64.8
通讯作者：
Cho, JH
中科院分区：
文献类型：
--
作者：
Ogura, Y;Bonen, DK;Cho, JH
克罗恩病是一种慢性胃肠道炎症性疾病，被认为是由环境因素对遗传易感宿主的影响造成的。通过多个连锁研究，已经确定了16号染色体周围中心区域IBD1的基因位置与克罗恩病的易感性有关（1-6），但尚未确定具体的基因。NOD2是一个编码与植物抗病基因产物同源蛋白的基因，位于16号染色体连锁的峰区（文献7）。通过传递不平衡测试和病例对照分析，我们发现胞嘧啶插入3020insC引起的移码突变与克罗恩病有关，该突变可能编码一个截断的NOD2蛋白。野生型NOD2激活核因子NF-kappaB，使其对细菌脂多糖产生反应；然而，突变体NOD2缺乏这种诱导。这些结果暗示NOD2与克罗恩病的易感性有关，并提示对细菌成分的先天免疫反应与疾病的发展之间存在联系。
Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, which is thought to result from the effect of environmental factors in a genetically predisposed host. A gene location in the pericentromeric region of chromosome 16, IBD1, that contributes to susceptibility to Crohn's disease has been established through multiple linkage studies(1-6), but the specific gene(s) has not been identified. NOD2, a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref. 7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease. Wild-type NOD2 activates nuclear factor NF-kappaB, making it responsive to bacterial lipopolysaccharides; however, this induction was deficient in mutant NOD2. These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease.