Gene Expression as Predictors of Outcome in the GENISOS (Genetics vs Environm

基因表达作为 GENISOS 结果的预测因子（遗传学与环境）

• 批准号: 7930522
• 负责人: Maureen Maureen Mayes
• 金额: $ 42.31万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7930522
• 关键词: African American; Arabidopsis; Autoantibodies; Autoimmune Process; Behavioral; Biopsy; Blood; Blood Vessels; Blood specimen; Caucasians; Caucasoid Race; Chronic Disease; Chronic Phase; Classification; Clinical; Custom; Data; Diffuse Scleroderma; Disease; Enrollment; Etiology; Fibrosis; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genetic screening method; Hispanics; Human; Individual; Language; Methods; Modeling; Molecular Profiling; Oligonucleotide Microarrays; Other Genetics; Outcome; Participant; Patients; Physicians; Printing; Pulmonary Fibrosis; Scleroderma; Serological; Skin; Systemic Scleroderma; Translational Research; clinical material; cohort; demographics; design; outcome forecast; peripheral blood; racial and ethnic; skin disorder; treatment planning

Systemic sclerosis (SSc) is a chronic disease characterized by fibrosis, vascular damage, and autoimmune phenomena. The etiology is unknown and the clinical spectrum is highly variable. Our study HYPOTHESIS is that prognosis in SSc can be predicted by gene expression profiling correlated with clinical, serologic and genetic/ethnic factors as well as sociodemographic features. Our SPECIFIC AIMS are as follows: 1) To perform classification analysis of peripheral blood gene-expression-profiles and skin biopsies from patients with early limited SSc, early diffuse SSc and matched healthy controls; 2) To compare these profiles in blood and skin biopsies from patients in the stable chronic phase of diffuse SSc to profiles from early, diffuse SSc both longitudinally (within individual patients) and in cross-sectional fashion (between separate patient groups); 3) to expand the multi-ethnic (Caucasian, Hispanic, and African-American) GENISOS early-disease SSc cohort following subjects longitudinally for disease relevant outcomes: 4) to characterize the cohort according to demographics, racial-ethnic background, clinical disease features, autoantibody subsets, HLA and other genetic testing, and socio-behavioral features; 5) To develop a model using the data from aims 1 through 4 to identify subsets of patients and predict prognosis; and 6) to provide clinical material from this cohort to support Project 1 of this CORT. DESIGN and METHODS: SSc patients with <5 years of disease will be enrolled and followed at defined intervals using standardized forms. Serial blood samples will be obtained on all and skin biopsies will be done on some participants. Custom printed 50-oligonucleotide microarrays representing 19,700 human and 208 Arabidopsis (negative controls) genes will be used and supervised methods and class comparison will be used to discover differentially regulated genes between predefined classes (e.g., early diffuse SSc vs late diffuse SSc).GEE analysis will be used to examine the association between the outcomes (e.g..course of skin disease, pulmonary fibrosis, etc.) and independent variables (e.g., demographic, HLA, microarray data, etc.) LAY LANGUAGE SUMMARY: This project will study patients with the recent onset of scleroderma in order to identify features that distinguish those who will have mild disease from those who will have a more severe course. This information will help physicians and patients decide on a treatment plan that is appropriate for their level of disease.

系统性硬化症（SSc）是一种以纤维化、血管损伤和自身免疫性疾病为特征的慢性疾病 现象。病因不明，临床谱高度可变。我们的研究假设是 可以通过与临床、血清学和免疫学相关的基因表达谱来预测SSc的预后。 遗传/种族因素以及社会人口特征。我们的具体目标如下：1） 对患者的外周血基因表达谱和皮肤活检进行分类分析 早期局限性SSc、早期弥漫性SSc和匹配的健康对照; 2）比较血液中的这些谱 从弥漫性SSc的稳定慢性期患者的皮肤活检到早期弥漫性SSc的轮廓 纵向（在个体患者内）和横截面方式（在单独的患者之间 群体）; 3）扩大多种族（白人，西班牙裔和非洲裔美国人）GENISOS早期疾病 SSc队列纵向跟踪受试者的疾病相关结局：4）表征队列 根据人口统计学、种族-民族背景、临床疾病特征、自身抗体亚群、HLA 和其他基因检测，以及社会行为特征; 5）使用目标1的数据开发模型 通过4来识别患者的子集并预测预后;以及6）从这一点提供临床材料 支持本次CORT的项目1。设计和方法：<5年的SSc患者 将使用标准化表格入组并在规定的时间间隔进行随访。一系列的血液样本 将对所有参与者进行皮肤活检。定制打印的50-寡核苷酸 将使用代表19，700个人类和208个拟南芥（阴性对照）基因的微阵列， 监督的方法和类比较将用于发现差异调节基因之间 预定义类（例如，早期弥漫性SSc vs晚期弥漫性SSc）。GEE分析将用于检查 结果之间的关联（例如，皮肤病病程、肺纤维化等）和独立 变量（例如，人口统计学、HLA、微阵列数据等）外行语言总结：该项目将 研究近期发生硬皮病的患者，以确定区分那些 将有轻微的疾病从那些谁将有一个更严重的过程。这些信息将帮助医生 患者决定适合其疾病水平的治疗方案。