Gene Polymorphisms Predisposing to Infectious Diarrhea

接触肠道病原体后，感染性腹泻的表现多种多样，取决于宿主和 致病因素。多种宿主因素调节感染的可能性或症状的严重程度，并可能 被归类为介导敏感性(即宿主遗传因素、病原体受体)和损伤(即， 刺激体液和电解质通道、促炎细胞因子)。感染的解决由以下因素决定 有助于控制和愈合阶段的因素(即抗炎细胞因子和特异性免疫)。 我们的中心假设是，导致一个或多个基因质量或数量差异的基因多态 这些介体中有几种对接触肠道后感染和疾病的发展负有部分责任 病原体。为此，我们将研究两个具有良好特征的感染性腹泻受试者群体。第一 研究小组将由来自发达国家前往细菌感染高危地区的健康成年人组成 治疗腹泻的药物。第二个研究组将由实验中接触隐孢子虫的健康成年人组成。 德克萨斯大学休斯顿临床研究中心。对于两者，我们建议研究宿主单核苷酸 编码蛋白质的基因的多态性(SNPs)与易感性、调节 疾病表现(损伤)、根除(对照)和感染后愈合。我们将重点关注三个代理， 具有不同病理生理学的水传播或食物传播途径的潜在生物恐怖主义用途；产肠毒素的大肠杆菌 分泌性腹泻、肠聚集性大肠杆菌、炎症性腹泻和隐孢子虫的病因 细胞内病原体。SNPs将与肠道病原体的分离和临床疾病相关。其影响 将在不同种族背景的背景下对SNPs进行审查。对结果的理解 感染与宿主遗传因素有关，在设计有针对性的生物防御干预措施时将是有用的。 朝着改进风险评估的方向发展。确定更易感染或易受艾滋病影响的人群 肠道病原体的影响在减少这些病原体可能造成的影响的策略设计中将是重要的。 在引发疾病和确定最有可能从预防、治疗和/或疫苗中受益的人群方面具有重要作用。

After exposure to an enteropathogen, the manifestations of infectious diarrhea are variable and depend on host and pathogen factors. A variety of host factors modulate the likelihood of infection or severity of symptoms and can be categorized as those that mediate susceptibility (i.e. host genetic factors, pathogen receptors), and injury (i.e. stimulation of fluid and electrolyte channels, pro inflammatory cytokines). Resolution of infection is determined by factors that contribute to the phases of control and healing (i.e. anti-inflammatory cytokines and specific immunity). Our central hypothesis is that genetic polymorphisms that lead to qualitative or quantitative differences in one or several of these mediators are partially responsible for the development of infection and illness after exposure to enteric pathogens. To this end we will study two well-characterized populations of subjects with infectious diarrhea. The first study group will consist of healthy adults traveling from developed nations to areas of risk for infection with bacterial agents of diarrhea. The second study group will consist of healthy adults experimentally exposed to Cryptosporidium at the University of Texas - Houston Clinical Research Center. For both we propose to investigate host single nucleotide polymorphisms (SNPs) of genes that encode proteins that are associated with either susceptibility, modulation of disease manifestation (injury), eradication (control) and healing after infection. We will focus on three agents with potential for bioterrorism use by waterborne or food borne routes with distinct pathophysiology; enterotoxigenic E. coli a cause of secretory diarrhea, Enteroaggregative E. colia cause of inflammatory diarrhea and Cryptosporidium an intracellular pathogen. SNPs will be correlated with the isolation of an enteropathogen and clinical illness. The impact of SNPs will be examined in the context of different ethnic backgrounds. The understanding of the outcome of infection as they relate to host genetic factors will be of use in designing biodefense interventions that are directed towards improving risk assessment. The identification of populations that are more susceptible or vulnerable to the effects of enteric pathogens will be important in the design of strategies to decrease the impact that these agents may have in causing disease and defining the populations most likely to benefit from prevention, treatment and or vaccines.