Novel genes and protein in non-alcoholic fatty liver disease: potential basis of a serum-based assessment of disease sta

非酒精性脂肪肝疾病中的新基因和蛋白质：基于血清的疾病状态评估的潜在基础

• 批准号: nhmrc : 252974
• 负责人: A/Pr Julie Jonsson
• 金额: $ 13.34万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Development Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/novel-genes-protein-disease-sta/98530
• 关键词: Novel; genes; protein; non; alcoholic

The most common cause of elevated liver function tests is non-alcoholic fatty liver disease (NAFLD). NALFD is a spectrum of disease ranging from steatosis, to non-alcoholic steatohepatitis (NASH), a condition associated with the development of fibrosis in the majority of individuals. Approximately 20% and 3% of adults are affected with NAFLD and NASH, respectively, and NAFLD is expected to become the next major liver epidemic facing the western world, far exceeding the prevalence of chronic infection with the hepatitis C virus. We obtained liver biopsies from patients with NAFLD, 80% of whom had NASH, and determined the expression profile analysis of each subject using 19,200 element microarrays. Our data demonstrates the concordant differential expression of 130 genes, in subjects with NAFLD that were categorizes into 6 major metabolic and regulatory pathways. Many of these genes represented uncharacterised genes. Utilising an extensive bioinformatics approach we have been able to define the genes and their protein product. The use of these proteins as a diagnostic tool for the detection of NAFLD forms the basis of a provisional patent application. However, measurements of protein levels in tissue and sera from patients with NAFLD are needed for the development of a diagnostic method. Such information would also provide significant insight into the pathogenesis of NAFLD. The AIMS are: 1)                  Production of antibodies against proteins encoded by candidate genes                  Expression profile of candidate genes 3)                  Expression of proteins encoded by candidate genes in patients with NAFLD

肝功能检查升高的最常见原因是非酒精性脂肪肝（NAFLD）。NALFD是从脂肪变性到非酒精性脂肪性肝炎（NASH）的一系列疾病，非酒精性脂肪性肝炎是与大多数个体中的纤维化发展相关的病症。大约20%和3%的成年人分别受到NAFLD和NASH的影响，预计NAFLD将成为西方世界面临的下一个主要肝脏流行病，远远超过丙型肝炎病毒慢性感染的流行率。我们从NAFLD患者（其中80%患有NASH）获得肝活检，并使用19，200个元件微阵列确定每个受试者的表达谱分析。我们的数据表明，在NAFLD受试者中，130个基因的一致差异表达被归类为6个主要的代谢和调节途径。这些基因中的许多代表了未表征的基因。利用广泛的生物信息学方法，我们已经能够定义基因及其蛋白质产物。使用这些蛋白质作为检测NAFLD的诊断工具构成了临时专利申请的基础。然而，需要测量来自NAFLD患者的组织和血清中的蛋白质水平以开发诊断方法。这些信息也将为NAFLD的发病机制提供重要的见解。目标是：1） 产生针对由候选基因编码的蛋白质的抗体 候选基因的表达谱3） 非酒精性脂肪肝患者候选基因编码蛋白的表达