Racial Difference in HCV-Host Interactions and Response

HCV-宿主相互作用和反应的种族差异

• 批准号: 7097979
• 负责人: TONY N. MARION
• 金额: $ 60.35万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7097979
• 关键词: African American; caucasian American; clinical research; cooperative study; hepatitis C; hepatitis C virus; human subject; racial /ethnic difference

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) is the etiologic agent of non-A, non-B hepatitis. HCV is now the most common cause of chronic liver disease in the United States and has surpassed alcoholic liver disease as the most common indication for liver transplantation in North America. An estimated 1.8% of all Americans are infected with a higher percentage among African Americans (AA). A hallmark of the disease is its chronicity with up to 85% of those exposed having chronic infection. The UTHSC Memphis Hepatitis C Cooperative Research Center was established to support clinical and basic research to understand the basis for chronic disease in HCV infection and response to therapy in clinically infected patients. The population of the greater Memphis area is 55% AA within which there is a significant problem with chronic HCV infection. The well documented poor response rate of AA to combination therapy exacerbates the obvious health problem of chronic HCV in this region. The primary research goal of the Memphis Hepatitis C Cooperative Research Center and this project is to understand why AA are more susceptible to chronic infection and why then response rate to combination therapy is only 50% or less of that for non AA patients. The project builds upon the success and achievements of the Center to implement a truly multidisciplinary approach for hypothesis-driven research to understand why there are racial differences in susceptibility to chronic disease and response to therapy. In addition, the program will seek to identify novel small molecule inhibitors that inhibit interaction between viral ligands or their receptors for development of a new generation of therapeutic modalities. The proposed research program for the Center includes two projects, an administrative core, and a clinical core. Project 1 will determine how HLA class II- dependent immune regulation and T cell specificities affect differences in immune responses to HCV and response to therapy in AA compared to non AA patients. Project 2 will determine if there is a difference in interferon-induced signaling between patients that respond to therapy and those that do not. Each project will require the patient resources provided by the outstanding clinical core.

描述（由申请人提供）：丙型肝炎病毒（HCV）是非甲非乙型肝炎的病原体。HCV现在是美国慢性肝病最常见的原因，并且已经超过酒精性肝病成为北美最常见的肝移植指征。据估计，所有美国人中有1.8%的人感染，非洲裔美国人（AA）的感染率更高。该疾病的一个特点是其慢性性，高达85%的接触者患有慢性感染。UTHSC孟菲斯丙型肝炎合作研究中心的成立是为了支持临床和基础研究，以了解HCV感染慢性疾病的基础和临床感染患者对治疗的反应。大孟菲斯地区的人口是55%的AA，其中慢性HCV感染是一个重大问题。AA对联合治疗的不良反应率加剧了该地区慢性HCV的明显健康问题。孟菲斯丙型肝炎合作研究中心和本项目的主要研究目标是了解为什么AA更容易受到慢性感染，以及为什么联合治疗的应答率仅为非AA患者的50%或更低。该项目建立在该中心的成功和成就的基础上，实施了一个真正的多学科方法，用于假设驱动的研究，以了解为什么在慢性病易感性和对治疗的反应方面存在种族差异。此外，该计划将寻求确定新的小分子抑制剂，抑制病毒配体或其受体之间的相互作用，以开发新一代的治疗方式。该中心的拟议研究计划包括两个项目，一个行政核心和一个临床核心。项目1将确定HLA II类依赖性免疫调节和T细胞特异性如何影响AA患者与非AA患者对HCV的免疫应答和对治疗应答的差异。项目2将确定对治疗有反应和无反应的患者之间干扰素诱导的信号传导是否存在差异。 每个项目都需要优秀的临床核心提供的患者资源。