RENAL DISEASE PROGRESSION GENES AND ENVIRONMENTAL IMPACT ON DIABETIC NEPHROPATHY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。糖尿病肾病（DN）是世界上导致慢性肾脏疾病的主要原因。虽然已经确定了一些可改变的风险因素，但来自高加索人和皮马印第安人的数据表明，DN是由遗传决定的。研究人员假设，中间表型，蛋白尿和肾小球滤过率（GFR）的变化，分别预测和衡量糖尿病肾病向终末期肾病（ESRD）的进展，是遗传的。这一假设将在非洲裔美国人（AA）和高加索家庭的纵向研究中得到验证，这将允许首次定义AA中DN的自然史。数据将通过定量性状位点（QLA）分析产生，这为正在进行的策略提供了优势，包括招募和更好地定义具有中间表型的DN受试者的临床病程（例如微量白蛋白尿），这些在以前的遗传分析中被排除在外。他们的糖尿病兄弟姐妹将进行表型分析和纵向跟踪。相关结果包括每年尿白蛋白排泄量和GFR测量。目标是900人其中450人在大都会医疗中心。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetic nephropathy (DN) is the leading cause of chronic renal disease in the world. Though some modifiable risk factors have been identified, data from Caucasians and Pima Indians indicate that DN is genetically determined. The investigators hypothesize that the intermediate phenotypes, proteinuria and glomerular filtration rate (GFR) change, which respectively predict and measure progression of diabetic nephropathy to End-Stage Renal Disease (ESRD), are heritable. The hypothesis will be tested in a longitudinal study of African American (AA) and Caucasian families, which will permit the natural history of DN in AA to be defined for the first time. Data will be generated by quantitative trait locus (QLA) analysis, which offers advantages to the ongoing strategies, including enrollment and better definition of the clinical course of DN subjects with intermediate phenotypes (e.g. microalbuminuria), which have previously been excluded in genetic analyses. Their diabetic siblings will be phenotyped and followed longitudinally. Dependent outcomes will include yearly urine albumin excretion and GFR measurements. Target accrual is 900 subjects with 450 at MetroHealth Medical Center.