THE GENETICS OF INFLAMMATORY BOWEL DISEASE

炎症性肠病的遗传学

• 批准号: 7604758
• 负责人: Dan Liviu Nicolae
• 金额: $ 3.17万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604758
• 关键词: Abdomen; Abdominal Pain; Affect; Caspase; Cell Wall; Characteristics; Chronic; Computer Retrieval of Information on Scientific Projects Database; Crohn' s disease; Development; Diarrhea; Disease; Disease susceptibility; Family; Funding; Genes; Genetic; Genetic Variation; Grant; Hemorrhage; Individual; Inflammation; Inflammatory Bowel Diseases; Inflammatory Response; Inheritance Patterns; Institution; Intestines; Leukocytes; Measures; Medical; Mutation; Operative Surgical Procedures; Patients; Peptidoglycan; Play; Purpose; Research; Research Personnel; Resources; Role; Source; Ulcerative Colitis; United States National Institutes of Health; Variant; genetic variant; improved; interest; member; mutant

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这些研究的目的是确定与炎症性肠病（IBD）相关的遗传变异。IBD是一种慢性肠道炎症，导致腹泻、肠道出血和腹痛。它由两种亚型组成，克罗恩病和溃疡性结肠炎。虽然药物治疗在过去几年中有所改善，但药物治疗仅部分有效，并且很大一部分IBD患者需要腹部手术。与IBD相关的遗传变异的鉴定可能有助于通过描述疾病发展机制来开发改进的，更具靶向的治疗方法。此类遗传研究包括追踪有多个成员受IBD影响的家庭的遗传模式，以及进行关联研究，其中比较患有和不患有IBD的无关个体之间遗传变异的携带情况。 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效应。IBD中特别感兴趣的是Nod 2（CARD 15，半胱天冬酶激活募集结构域）基因中的遗传变异。对携带和不携带相关突变的个体的白色血细胞进行研究。对于Nod 2突变，测量对细菌肽聚糖组分（其细胞壁的组分）的炎症反应。Nod 2突变型白色血细胞的短期刺激与降低的炎症反应相关。正在进行研究，以检查肠道细菌刺激特性的慢性影响。