GENETICS OF THE DUODENAL ULCER DISEASES

十二指肠溃疡疾病的遗传学

• 批准号: 3231737
• 负责人: DAVID L RIMOIN
• 金额: $ 23.65万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1988-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3231737
• 关键词: ABO(H) blood groups; autoimmune disorder; cytogenetics; developmental genetics; duodenum; extrachromosomal DNA; gastrointestinal disorder diagnosis; genetic disorder diagnosis; genetic markers; human subject; linkage mapping; pepsinogens; population genetics; ulcer

This proposal is directed toward the elucidation of the genetic susceptibility to the duodenal ulcer diseases using subclinical and polymorphic genetic markers. Though genetic factors have been acknowledged to play a role in the etiology of duodenal ulcer, only recently have promising subclinical markers and genetic heterogeneity been recognized. We propose to confirm and extend our preliminary findings that duodenal ulcer is genetically heterogeneous and can be separated into more homogeneous disorders by the study of subclinical markers in families. We propose, over a 4-year period, to study 200 duodenal ulcer patients and 800 of their first degree relatives for the most promising subclinical and genetic markers presently available - serum pepsinogen I and II, fasting and stimulated gastrin, ABO blood type, secretor status, urinary pepsinogen phenotype, alpha-1-antitrypsin, gastric emptying, and thyrogastric antibodies. By identifying the aggregation of the subclinical markers, and performing segregation and linkage analyses we will: 1) test if duodenal ulcer is genetically heterogenous and can be separated into more homogeneous subgroups using subclinical and genetic markers in families, 2) examine the mode of inheritance of the more specific subgroups, 3) determine whether any of the gene marker associations, blood group 0, nonsecretor status, urinary pepsinogen phenotype A, alpha-1-antitrypsin, are more prominent within specific subgroups, 4) perform genetic marker linkage analysis on the specific duodenal ulcer subgroups with the four gene marker systems, and 5) test the hypothesis of an immunologic form of duodenal ulcer by examining whether subclinical markers of gastritis are found in duodenal ulcer families. Thus, these studies are directed toward verification of our preliminary evidence for genetic heterogeneity of the duodenal ulcer diseases, and toward determination of the mode(s) of inheritance of each component disorder. The ultimate goal of these studies is to develop the means of identifying those individuals in the population who are at genetically high risk for duodenal ulcer. The resultant subclinical markers will be invaluable for the investigation of individual pathogenetic mechanisms, for the study of the interaction of genetic and environmental factors, and for the development of more specific modes of therapy and prevention.

该提议针对遗传的阐明 使用亚临床和 多态性遗传标记。 尽管已经确认了遗传因素 要在十二指肠溃疡的病因中发挥作用，直到最近才 认识到有希望的亚临床标记和遗传异质性。 我们建议确认并扩展我们的初步发现十二指肠 溃疡在遗传上是异质的，可以分为更多 通过研究家庭中亚临床标记的均质疾病。 我们 在4年内，建议研究200名十二指肠溃疡患者和800例 最有前途的亚临床和 目前可用的遗传标记 - 血清胃蛋白原I和II，禁食 和刺激胃蛋白，ABO血型，分泌剂状态，尿脱蛋白酶原 表型，α-1-抗胰蛋白酶，胃排空和甲状胃 抗体。 通过识别亚临床标记的聚合，以及 执行分离和链接分析我们将：1）测试如果十二指肠 溃疡在遗传上是异质的，可以分为更多 使用亚属性和遗传标记的均质亚组，2） 检查更具体的亚组的继承方式，3） 确定是否有任何基因标记关联，血液组0， 非分类状态，尿脱蛋白酶原表型A，α-1-抗抗蛋白酶， 在特定亚组中更为突出，4）执行遗传标记 与四个的特定十二指肠溃疡亚组的连锁分析 基因标记系统和5）检验一种免疫学形式的假设 十二指肠溃疡通过检查胃炎的亚临床标志物是否是 在十二指肠溃疡家庭中发现。 因此，这些研究针对 验证我们的初步证据证明了遗传异质性 十二指肠溃疡疾病，朝着确定的模式 每个组件障碍的遗传。 这些研究的最终目标 是开发确定人口中那些人的手段 十二指肠溃疡的遗传风险很高。 结果 亚临床标记对于个人的研究将是无价的 致病机制，用于研究遗传与 环境因素，以及开发更具体的模式 治疗和预防。