GENETIC STUDIES OF CROHN'S DISEASE AND ULCERATIVE COLITIS

克罗恩病和溃疡性结肠炎的遗传学研究

• 批准号: 6275620
• 负责人: STEVEN BRANT
• 金额: $ 2.01万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6275620
• 关键词: Crohn's disease; clinical chemistry; clinical research; family genetics; gene expression; genetic susceptibility; genotype; human genetic material tag; human subject; linkage mapping; molecular pathology; ulcerative colitis

The inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are chronic frequently disabling inflammatory disorders of the small and large intestines. Despite extensive immunologic, pathologic and microbiologic reseerch, the etiology remains unknown, and the pathophysiology is poorly understood. Medical therapy is suboptimal and often associated with considerable morbidity. The risk of colorectal cancer is significantly increased for both disorders. There is strong evidence from twin studies, studies of familial aggregation and ethnic differences in disese prevalence that the inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are in large part genetic. The disorders are categorized as complex genetic disorders, since inheritance does not follow simple Mendelian patterns. In comparison with other complex genetic disorders the degree of genetic clustering in siblings, expressed as ns and defined as the increased risk over population prevalence for a sibling of a proband, is relatively large. ns for CD, UC and IBD have been estimated at 36.5, 16.6 and 24.7, respectively, comparatively greater than that for other disorders where susceptibility genes have been better established, such as IDDM and schizophrenia where ns is 15 and 8.6, respectively. CD and UC are genetically related as the cross disease relative risk is 3.85 with a CD proband and 1.72 with a UC proband. Our genetic studies on IBD are based on the hypothesis that there are specific susceptibility genes which are responsible for the familial clustering of these diseases. Susceptibility gene identification will allow an understanding of the initial pathophysiologic mechanisrns, and thus make it possible to design better medical therapy and better predict the disease course.

炎症性肠病、克罗恩病和溃疡性结肠炎， 是慢性经常致残性炎症性疾病的小， 大肠尽管广泛的免疫，病理和 微生物学研究，病因仍然未知， 病理生理学知之甚少。药物治疗不理想， 通常与相当大的发病率有关。结肠直肠癌的风险 这两种疾病的癌症显著增加。 有强有力的证据来自双胞胎研究， 疾病流行率的聚集和种族差异， 炎症性肠病（IBD）、克罗恩病（CD）和溃疡性结肠炎（UC） 结肠炎（UC）在很大程度上是遗传性的。这些疾病被分类为 复杂的遗传疾病，因为遗传并不遵循简单的 孟德尔模式。与其他复杂的遗传疾病相比， 兄弟姐妹的遗传聚集程度，表示为NS和 定义为兄弟姐妹的患病风险高于人群患病率 先证者的遗传变异相对较大 对于CD、UC和IBD， 估计分别为36.5、16.6和24.7， 而对于其他疾病，易感基因 更好地建立，如胰岛素依赖型糖尿病和精神分裂症，其中ns为15， 8.6分别。CD和UC在遗传上是交叉相关的 CD先证者的疾病相对风险为3.85，UC为1.72 先证者 我们对IBD的遗传学研究是基于以下假设： 特定的易感基因，负责家族性 这些疾病的聚集。易感基因鉴定将 允许理解最初的病理生理机制，和 从而使设计更好的医学治疗成为可能， 预测疾病进程。