GENETIC EPIDEMIOLOGY OF TUBERCULOSIS SUSCEPTIBILITY

结核病易感性的遗传流行病学

• 批准号: 2005705
• 负责人: James MALLORY Musser
• 金额: $ 48.27万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2005705
• 关键词: Mycobacterium tuberculosis; bacterial genetics; chemical fingerprinting; child (0-11); clinical research; disease /disorder proneness /risk; genetic polymorphism; genotype; host organism interaction; human population genetics; human subject; immunogenetics; international cooperation; microorganism immunology; pediatrics; respiratory disorder epidemiology; tuberculosis; tumor necrosis factor alpha

DESCRIPTION: (Adapted from Applicant's Abstract). The long-tern objective of this research is to determine the extent to which human genetic variability contributes to TB susceptibility and to the character of the resulting disease. To avoid pitfalls associated with previous work in this field, these questions will be examined at the nucleotide level in approximately 250-300 pediatric patients assigned to precisely defined clinical disease categories. The study population will be pediatric TB patients living in Houston, TX, a city with the highest reported rate of childhood TB in the U.S. Genotyping strategies, already employed successfully in the laboratories of this international collaborative study group will be used to determine the association of TB in pediatric patients with polymorphisms in four candidate susceptibility loci: NRAMPI (encoding a macrophage membrane protein critical in mediating murine susceptibility to BCG infection); TNFA (encoding the cytokine tumor necrosis factor-alpha); MBL (encoding mannose binding protein); and VDR (encoding the Vitamin D receptor). New, state-of-the-art molecular strategies will also be used to conduct a genome-wide screen to identify loci not previously associated with human TB susceptibility. All M.tuberculosis case isolates will be analyzed molecularly to test the hypothesis that distinct pathogen genotypes are non-randomly associated with certain host genotypes (i.e., the potential role of host-pathogen genotypic combinations in mediating disease character will be examined). By wedding analysis of host and pathogen molecular data with clinicopathologic correlates of afflicted patients, the proposed study is intended to contribute new insights into host-pathogen relationships.

描述：（改编自申请人的摘要）。 长期目标 这项研究的是确定人类遗传的程度 可变性有助于结核病的敏感性和特征 由此产生的疾病。 为了避免与以前的工作相关的陷阱 字段，将在核苷酸水平上检查这些问题 分配给精确定义的大约250-300名儿科患者 临床疾病类别。 研究人群将是小儿结核 居住在德克萨斯州休斯顿的患者，这是一个报告最高的城市 美国基因分型策略中的儿童结核病，已经使用 在这项国际合作研究的实验室中成功 小组将用于确定小儿患者结核病的关联 在四个候选敏感性基因座中的多态性：NRAMPI（编码） 巨噬细胞膜蛋白在介导鼠的易感性时至关重要 BCG感染）； TNFA（编码细胞因子肿瘤坏死因子-Alpha）； MBL（编码甘露糖结合蛋白）；和VDR（编码维生素D 受体）。 新的，最先进的分子策略也将用于 进行全基因组屏幕以识别以前与之相关的基因座 人类结核病的敏感性。 将分析所有大麻结核病病例分离株 分子检验以下假设：不同的病原体基因型是 与某些宿主基因型相关的非随机 宿主 - 病原体基因型组合在介导疾病特征中的作用 将被检查）。 通过宿主和病原体分子数据的婚礼分析 拟议的研究随着患者的临床病理相关性 旨在为宿主病原体关系提供新的见解。