Case FIND Participating Investigative Center

描述（由申请人提供）： 在过去的十年中，终末期肾病（ESRD）的发病率每年增加约8%。糖尿病肾病是慢性肾病的主要原因，占ESRD病例的40%以上。虽然已经确定了可改变的危险因素，但流行病学数据表明糖尿病肾病是由遗传决定的，有多个基因调节表型。肾病和糖尿病家族调查（FIND）是一项多中心研究，旨在确定糖尿病肾病的遗传决定因素。它正在美国的八个参与调查中心和一个协调中心进行，有四个族裔群体（欧洲裔美国人、非洲裔美国人、墨西哥裔美国人和美洲印第安人）。两种分析策略被用来定位易感基因座：一个以家庭为基础的连锁研究和一个病例对照研究使用混合连锁不平衡作图。在第一个资助周期中，Case PIC招募了非裔美国人和欧洲裔美国人家庭进行FIND家庭研究，使用财团商定的表型标准。家族研究病例PIC部分的招募目标为284个同胞对（138个AA ASP、38个高加索ASP、92个AA DSP和21个高加索DSP）。在入组期结束时，我们筛选了2，854例受试者，招募了283对同胞对，细分包括115例AA ASP、59例高加索ASP、50例AA DSP、59例高加索DSP。肾病与糖尿病的其他终末器官、微血管并发症（如视网膜病变和神经病变）之间存在很强的一致性。然而，来自Pima的样本的基因组扫描表明，肾病和视网膜病变表型的一些连锁峰是一致的，而其他的则不同，这表明了不同的遗传调控机制。除了收集糖尿病和肾病表型受试者外，病例PIC还获得了补充资金，用于使用7个视网膜视野的立体照片进行糖尿病视网膜病变的表型FIND参与者。要求病例PIC招募120名FIND先证者和适当的同胞。到目前为止，病例PIC已经招募了106名先证者和180对同胞。作为FIND的参与者，Case PIC为组装一个大型且表型良好的糖尿病患者队列做出了贡献，该队列将用于确定糖尿病微血管疾病的遗传基础。案例PIC有两个继续供资的目标。首先，病例研究者将参与糖尿病表型和遗传数据的分析以及FIND家族研究的手稿准备。这些研究将由案例PIC与GADCC和其他PIC一起进行。其次，病例PIC将继续招募104名符合条件的FIND视网膜病FIND受试者并进行表型分析。

DESCRIPTION (provided by applicant): The incidence of end stage renal disease (ESRD) has increased by approximately 8% per year for the past decade. Diabetic nephropathy is the leading cause of chronic renal disease, accounting for over 40% of incident ESRD cases. Although modifiable risk factors have been identified, epidemiologic data indicate that diabetic nephropathy is genetically determined, with multiple genes regulating the phenotype. The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter study to identify genetic determinants of diabetic nephropathy. It is being conducted in eight U.S. participating investigative centers (PIC) and a coordinating center, with four ethnic groups (European Americans, African Americans, Mexican Americans and American Indians). Two analytic strategies are being used to localize susceptibility loci: a family-based linkage study and a case-control study using mapping by admixture linkage disequilibrium. During the first funding cycle, the Case PIC recruited both African American and European American families for the FIND Family Study, using phenorype criteria agreed upon by the consortium. The recruitment target for the Case PIC portion of the family study was 284 sib pairs (138 AA ASP, 38 Caucasian ASP, 92 AA DSP and 21 Caucasian DSP). At the end of the enrollment period, we had screened 2,854 subjects, resulting in the recruitment of 283 sib pairs, with the breakdown including 115 AA ASP, 59 Caucasian ASP, 50 AA DSP, 59 Caucasian DSP. There is strong concordance between nephropathy and other end-organ, microvascular complications of diabetes, such as retinopathy and neuropathy. However, a genome scan of samples from the Pima demonstrated some linkage peaks for nephropathy and retinopathy phenotypes were coincident, whereas others differed, suggesting separate genetic regulatory mechanisms. In addition to collection of subjects with diabetes and nephropathy phenotypes, the Case PIC received supplemental funding to phenotype FIND participants for diabetic retinopathy using stereoscopic photographs of seven retinal fields. The Case PIC has been asked to recruit 120 FIND probands and appropriate sibs. To date, the Case PIC has enrolled 106 probands and 180 sib pairs. As participants in FIND, the Case PIC has contributed to the assembly of a large and well-phenotyped cohort of diabetics, which will be used to determine the genetic basis for diabetic microvascular diseases. The Case PIC has two aims for continuation funding. First, the Case investigators will participate in analyses of the diabetic phenotypic and genetic data and manuscript preparation for the FIND family study. These studies will be done by the Case PIC in conjunction with the GADCC and the other PICs. Second, the Case PIC will continue recruitment and phenotyping of 104 eligible FIND participants for FIND Retinopathy.