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.
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