The purpose of this study is to identify the genes causing diabetic and non- diabetic renal failure (RF) in high risk black and white families residing in the southeastern United States.. Diabetes is the most common cause of end- stge renal disease (ESRD) in the U.S.. At most, 30% of diabetic patients are susceptible to RF with its progression to ESRD and high mortality rate. Selected diabetic families demonstrate multi-generational clustering of renal disease. An inherited basis for RF is also supported by reports that blacks are more likely than whites to develop RF. These racial differences are not fully explained by racial differences in prevalence or severity pf diabetes mellitus or hypertension, socioeconomic factors or access to healthcare. In order to identify genes causing RF we will continue to identify, clinically characterize, and collect DNA from 400 families (200 black, 200 white) with type 2 diabetic ESRD index cases and additional first degree relatives with type 2 diabetes mellitus. This phase of the project employs the unique """"""""Family History orf relatives with type 2 diabetes mellitus. This phase of the project employs the unique """"""""Family History of ESRD"""""""" database, independently compiled by the federally-funded ESRD Network 6 (Southeastern Kidney Council). This registry currently contains family history data from more than 20,00 incident patients with ESRD who started dialysis after September, 1993. Approximately 60% of patients are black and 40% have diabetic RF. Candidate genes will be screened for linkage to RF at the Wake Forest University Baptist Medical Center, and DNA and clinical data will also be supplied to the study's Genetic Analysis and Data Coordinating Center (GADCC) for a comprehensive genome wide survey to identify novel loci causing RF. The identification of RF genes would form a genetic basis for detection of high risk individuals and lead to the development of intervention and treatment strategies for prevention of kidney disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DK057298-02S1
Application #
6447373
Study Section
Special Emphasis Panel (ZDK1 (O1))
Program Officer
Rasooly, Rebekah S
Project Start
1999-09-30
Project End
2004-09-29
Budget Start
2000-09-30
Budget End
2001-09-29
Support Year
2
Fiscal Year
2001
Total Cost
$35,000
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
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
Freedman, Barry I; Murea, Mariana (2010) Potential effects of MYH9-associated nephropathy on dialysis and kidney transplant outcomes. Semin Dial 23:244-7
Sedor, John R; Freedman, Barry I (2010) Genetics and the kidney: promise, potential, and challenges. Introduction. Semin Nephrol 30:99-100
Freedman, Barry I; Parekh, Rulan S; Kao, W H Linda (2010) Genetic basis of nondiabetic end-stage renal disease. Semin Nephrol 30:101-10
Bleyer, Anthony J; Sedor, John R; Freedman, Barry I et al. (2008) Risk factors for development and progression of diabetic kidney disease and treatment patterns among diabetic siblings of patients with diabetic kidney disease. Am J Kidney Dis 51:29-37

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