Diabetic Nephropathy is the leading cause of end stage renal failure in the United States. Statistics indicate that certain ethnic groups, such as Mexican Americans, Pima Indians and African Americans are disproportionately affected by diabetes and its complications including diabetic nephropathy and diabetic retinopathy. Studies done in Pima Indians have demonstrated strong evidence for the presence of genetic factors that may determine susceptibility to develop these complications. The Family Investigation of Nephropathy and Diabetes (FIND), which began in 1999, was designed to identify some of the genetic determinants of both Diabetic Nephropathy and Diabetic Retinopathy in several ethnic groups. The UCLA Participating Investigator Center (PIC) has been responsible primarily for recruitment of Mexican Americans into the study. The UCLA PIC has consistently been a major contributor to the overall recruitment population of the FIND study. As of January 2005, Dr. Susanne B. Nicholas, upon the request of the NIH/NIDDK and approval of the Executive Chair of the UCLA Department of Medicine has assumed the position of Principal Investigator of the UCLA FIND Study. One of the specific aims of the proposal is to complete the goals of the original FIND project. This will entail activities such as data cleaning, completion of phenotyping for families that are currently enrolled in the Retinopathy Study but are missing medical record information or laboratory data that will resolve their eligibility for the study. It will also involve recall of subjects and redraw of blood samples for DNA extraction. We also propose to use stored frozen blood for whole genome amplification of DNA by Phi29 rolling circle DNA replication. This in vitro process will facilitate the production of high-fidelity DNA that can be used for genotyping in the event of participant mortality or loss of follow-up. This will maintain the integrity of the central database. Since recruitment of African Americans into the study has been overall low, we propose to recruit African Americans for the Mapping Admixture Linkage Disequilibrium (MALD) study. Working in conjunction with the other PICs, a Candidate gene grant application based on the candidate genes obtained so far will be submitted. The final year of the project will focus more heavily on manuscript preparation. Dr. Nicholas will be directly involved in all aspects of the project.
