THE GENETICS OF INFLAMMATORY BOWEL DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这些研究的目的是确定与炎症性肠病(IBD)相关的基因变异。IBD是一种慢性肠道炎症，会导致腹泻、肠道出血和腹痛。它由两个亚型组成，克罗恩S病和溃疡性结肠炎。虽然医学疗法在过去几年中有所改善，但医学疗法只有部分有效，相当一部分IBD患者需要进行腹部手术。识别与IBD相关的遗传变异可能有助于通过描绘疾病发展的机制来开发改进的、更有针对性的治疗方法。这类遗传研究包括跟踪有一名以上成员受IBD影响的家庭的遗传模式，以及进行关联研究，比较患有IBD和不患有IBD的无关个体携带的基因变异。 那些被认为在疾病易感性中起直接作用的遗传变异将被进一步检查，以确定所讨论的特定变异的功能影响。对IBD特别感兴趣的是NOD2(CARD15，半胱氨酸天冬氨酸氨基转移酶激活招募结构域)基因的遗传变异。对携带和不携带相关突变的个体的白细胞进行研究。对于NOD2突变，测量对细菌肽聚糖成分(它们细胞壁的一种成分)的炎症反应。短期刺激NOD2突变的白细胞与减少炎症反应有关。检查肠道细菌刺激特征的慢性影响的研究正在进行中。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of these studies is to identify the genetic variants that are associated with inflammatory bowel disease (IBD). IBD is a chronic inflammation of the intestines and results in diarrhea, intestinal bleeding, and abdominal pain. It is comprised of two subtypes, Crohn s disease and ulcerative colitis. While medical therapies have improved over the past several years, medical therapies are only partially effective and a significant fraction of IBD patients require abdominal surgery. The identification of genetic variants that are associated with IBD may assist in the development of improved, more targeted therapies by delineating mechanisms of disease development. Such genetic studies have included tracking inheritance patterns in families with more than one member affected by IBD, as well as performing association studies where carriage of genetic variants are compared between unrelated individuals with and without IBD. Those genetic variants which are believed to play a direct role in disease susceptibility will then be further examined to define the functional effects of a particular variant in question. Of particular interest in IBD are genetic variation in the Nod2 (CARD15, caspase activation recruitment domain) gene. Studies in white blood cells from individuals carrying and not carrying the relevant mutations are performed. For Nod2 mutations, inflammatory responses to components of bacterial peptidoglycan (a component of their cell walls) are measured. Short term stimulation of Nod2 mutant white blood cells is associated with a reduced inflammatory response. Studies to examine chronic effects of bacterial stimulation characteristic of the intestine are ongoing.