RENAL DISEASE PROGRESSION GENES AND ENVIRONMENTAL IMPACT ON DIABETIC NEPHROPATHY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。糖尿病肾病（diabetic nephropathy，DN）是世界范围内慢性肾脏病的主要病因。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，分别预测和测量糖尿病肾病进展为终末期肾病（ESRD），是可遗传的。这一假设将在一项对非裔美国人（AA）和高加索人家庭的纵向研究中进行检验，这将首次定义AA中DN的自然史。将通过数量性状基因座（QLA）分析生成数据，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（例如微量白蛋白尿）的DN受试者的临床病程，这些表型先前已被排除在遗传分析之外。 他们的糖尿病兄弟姐妹将表型和纵向跟踪。依赖性结局将包括每年尿白蛋白排泄和GFR测量。目标入组人数为900例受试者，其中450例在MetroHealth Medical Center。

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.