GENETIC RISK PROFILE IN LONGITUDINAL SLE COHORTS

纵向 SLE 队列中的遗传风险概况

• 批准号: 6201555
• 负责人: Graciela S Alarcon
• 金额: $ 19.12万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6201555
• 关键词: clinical research; family genetics; gene expression; genetic susceptibility; genotype; human subject; longitudinal human study; patient /disease registry; phenotype; systemic lupus erythematosus

Both genetic and non-genetic factors contribute to the clinical presentations, clinical course, and outcome in SLE. To develop the theme of this SCOR, the genetics of SLE, and to translate the findings to the bedside by characterizing the clinical manifestations associated with the identified genetic markers, we propose to gather a population of well characterized SLE patients by joining efforts with investigators who already have ESTABLISHED longitudinal cohorts and the mechanisms to enroll NEW patients (Drs. Petri, John Hopkins University, MD; Reveille, University of Texas Health Sciences Center, Houston, TX; Ramsey-Goldman, Northwestern University, Chicago, IL) which will constitute the largest single available cohort of SLE patients for such studies (The PROFILE cohort)> With this cohort we will determine the extent to which a given genotype (PROFILE) determines the clinical phenotype. We will also contribute to the constitution of TRIO families for TDT analysis in order to confirm and narrow regions of genetic interest. The specific aims of the study are to: 1) Establish a multi-center common core database of SLE patients from multiple ethnicities comprised of patients who are already in local cohorts (ESTABLISHED) as well as NEW patients to be recruited; 2) Assess the ability of chromosome 1 genes (q21-32, see projects #1-3) to predict disease phenotype [renal, cardiovascular, pulmonary, and central nervous system, (CNS) involvement] in this PROFILE COHORT of SLE patients; 3) Establish a core set of TRIO families and work in conjunction with projects #1-3 and the Genetic Epidemiology and Biostatistics Core to use transmission disequilibrium to confirm the identification of candidate regions and genes in SLE. We have based our power and sample size calculations on the frequency of FcgammaRII H131/H131 in SLE patients with and without renal disease (8% versus 20%) and the frequency of renal disease among lupus patients from one of the center's cohorts. With total number of SLE patients of 600-700, we will have adequate power to demonstrate the skewing of this and other genes in the phenotype of the disease. Descriptive and analytical methods will be used where the phenotype will be the dependent variable and genetic (and other factors) the independent variables. The ability to predict the expression of the disease may have important implications for optimizing therapeutic strategies or developing new therapies for lupus patients.

遗传和非遗传因素都有助于临床 SLE的临床表现、临床病程和结局。展开主题 SLE的遗传学，并将研究结果转化为 床旁通过表征与 确定了遗传标记，我们建议收集一个人口以及 通过与研究者合作， 已经建立了纵向队列和招募机制 新患者（Petri博士，约翰霍普金斯大学，医学博士; Reveille， 德克萨斯大学健康科学中心，德克萨斯州休斯顿;拉姆齐-戈德曼， 西北大学，芝加哥，IL），这将构成最大的 用于此类研究的单一可用SLE患者队列（PROFILE 我们将在这个群体中确定给定的 基因型（PROFILE）决定临床表型。我们还将 有助于TDT分析的TRIO族的构建， 来确认和缩小基因区域。的具体目标 本研究主要目的是：1）建立多中心SLE共同核心数据库 来自多个种族的患者，包括已经 在当地队列（已建立）以及待招募的新患者中; 2） 评估1号染色体基因（q21 - 32，见项目1 - 3）的能力， 预测疾病表型[肾、心血管、肺和中枢神经系统 神经系统（CNS）受累]; 3)建立一套核心的TRIO系列，并与 项目#1 - 3和遗传流行病学和生物统计学核心使用 传递不平衡，以确认候选人的身份 区域和基因。 我们的功效和样本量计算基于以下频率： FcgammaRII H131/H131在有和无肾脏疾病的SLE患者中（8%） 与20%）和狼疮患者中肾脏疾病的频率 中心的一个同伙SLE患者总数为600 - 700例， 我们将有足够的力量来证明这个和其他的倾斜 疾病表型中的基因。描述和分析方法 当表型为因变量时， 遗传（和其他因素）是独立变量。的能力 预测疾病的表达可能对 优化治疗策略或开发狼疮的新疗法 患者