GENETIC RISK PROFILE IN LONGITUDINAL SLE COHORTS

纵向 SLE 队列中的遗传风险概况

• 批准号: 6348946
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6348946
• 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的演示，临床课程和结果。发展主题 在这个SCOR中，SLE的遗传学，并将发现转化为 通过表征与 确定的遗传标记，我们建议收集一口井 通过与调查员一起努力来表征SLE患者 已经建立了纵向队列和注册的机制 新患者（约翰·霍普金斯大学，马里兰州彼得里博士； 德克萨斯州休斯顿市德克萨斯大学健康科学中心；拉姆齐·戈尔曼（Ramsey-Goldman）， 伊利诺伊州芝加哥西北大学，将构成最大的 单一可用的SLE患者进行此类研究（概况 队列）>使用此队列，我们​​将确定给定的程度 基因型（轮廓）确定临床表型。我们也会 为TDT分析的三人家族的构成做出贡献 确认和狭窄的遗传利益区域。具体目的 该研究是：1）建立SLE的多中心通用核心数据库 来自已有多种种族的患者 在当地队列（已建立）以及将要招募的新患者； 2） 评估染色体1基因的能力（Q21-32，请参见项目＃1-3） 预测疾病表型[肾脏，心血管，肺和中央 神经系统，（CNS）参与] SLE患者的概况组； 3）建立一组三人家庭，并与 项目＃1-3以及要使用的遗传流行病学和生物统计学核心 传播不平衡以确认候选人的识别 SLE中的区域和基因。 我们的功率和样本量计算基于 SLE患有和没有肾脏疾病的SLE患者的Fcgammarii H131/H131（8％ 与20％）以及来自狼疮患者的肾脏疾病频率 该中心的同伙之一。 600-700的SLE患者总数 我们将拥有足够的力量来证明这一和其他的偏斜 疾病表型中的基因。描述性和分析方法 将在表型为因变量和 遗传（和其他因素）自变量。能力 预测疾病的表达可能对 优化治疗策略或为狼疮开发新疗法 患者。