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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01DK057303-06
Application #
7036303
Study Section
Special Emphasis Panel (ZDK1-GRB-3 (O1))
Program Officer
Rasooly, Rebekah S
Project Start
1999-09-30
Project End
2007-08-31
Budget Start
2005-09-30
Budget End
2006-08-31
Support Year
6
Fiscal Year
2005
Total Cost
$175,000
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Williams, Robert C; Elston, Robert C; Kumar, Pankaj et al. (2016) Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND). BMC Genomics 17:325
Iyengar, Sudha K; Sedor, John R; Freedman, Barry I et al. (2015) Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND). PLoS Genet 11:e1005352
Ng, Maggie C Y; Shriner, Daniel; Chen, Brian H et al. (2014) Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. PLoS Genet 10:e1004517
Sandholm, Niina; McKnight, Amy Jayne; Salem, Rany M et al. (2013) Chromosome 2q31.1 associates with ESRD in women with type 1 diabetes. J Am Soc Nephrol 24:1537-43
Bostrom, Meredith A; Kao, W H Linda; Li, Man et al. (2012) Genetic association and gene-gene interaction analyses in African American dialysis patients with nondiabetic nephropathy. Am J Kidney Dis 59:210-21
Igo Jr, Robert P; Iyengar, Sudha K; Nicholas, Susanne B et al. (2011) Genomewide linkage scan for diabetic renal failure and albuminuria: the FIND study. Am J Nephrol 33:381-9
Nicholas, Susanne B; Basgen, John M; Sinha, Satyesh (2011) Using stereologic techniques for podocyte counting in the mouse: shifting the paradigm. Am J Nephrol 33 Suppl 1:1-7
Bostrom, Kristina I; Jumabay, Medet; Matveyenko, Aleksey et al. (2011) Activation of vascular bone morphogenetic protein signaling in diabetes mellitus. Circ Res 108:446-57
Adler, Sharon; Pahl, Madeleine; Abboud, Hanna et al. (2010) Mexican-American admixture mapping analyses for diabetic nephropathy in type 2 diabetes mellitus. Semin Nephrol 30:141-9