GENETIC RISK PROFILE IN LONGITUDINAL SLE COHORTS

遗传和非遗传因素共同作用于临床 系统性红斑狼疮的临床表现、病程和转归。来发展这个主题 这个SCOR，SLE的遗传学，并将发现转化为 通过描述与本病相关的临床表现 经过鉴定的遗传标记，我们建议收集一个井的种群 SLE患者的特征是与调查人员共同努力 已经建立了纵向队列和招生机制 新患者(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，伊利诺伊州)，这将构成最大的 用于此类研究的单一可用SLE患者队列(简介 队列)&gt；有了这个队列，我们将确定给定的 基因型别决定了临床表型。我们还将 为有序的TDT分析贡献三个家庭的组成 以确认和缩小基因兴趣区。的具体目标 1)建立系统性红斑狼疮多中心共用核心数据库 来自多个种族的患者包括已经 在当地队列中(已建立)以及将招募的新患者；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[肾脏、心血管、肺脏和中枢 神经系统(CNS)受累]在SLE患者的这一队列中； 3)建立一套核心的三人家庭，并与 项目#1-3和遗传流行病学和生物统计学核心使用 确认候选人身份的传递不均衡 系统性红斑狼疮的区域和基因。 我们的功率和样本量计算基于以下频率 FcGammaRII H131/H131在伴有和不伴有肾脏疾病的SLE患者中的表达(8%) 与20%相比)和狼疮患者的肾脏疾病频率 该中心的一群人。系统性红斑狼疮患者总数为600-700人， 我们将有足够的力量来证明这个和那个的歪曲 疾病表型中的基因。描述性和分析性方法 将在表型为因变量的情况下使用，并且 遗传(和其他因素)的自变量。有能力 预测这种疾病的表现可能会对 优化治疗策略或开发狼疮新疗法 病人。

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.