The purpose of this study is to identify genes causing hypertension-associated end-stage renal disease (HESRD) in the high risk African American population. Inherited and environmental factors likely contribute to the racially variable pattern of both hypertension and H-ESRD. Although hypertensives only rarely develop hypercreatinemia, select African American families demonstrate strong multi-generational clustering of HESRD. An inherited basis for H-ESRD is also supported by reports that racial differences in socio-economic status, access to medical care and prevalence of diabetes and hypertension do not fully account for the excess risk of H-ESRD observed in African Americans. In order to identify genes causing H-ESRD we will continue to identify, clinically characterize, and collect DNA from African American sibling pairs (and other family members) with H-ESRD. This phase of the project employs Dr. Freedman's unique """"""""Family History of ESRD"""""""" database, independently collected by the federally-funded ESRD Network 6. This registry will contain family history data on 8,00() incident African American ESRD patients, by September, 1996. Initially, candidate genes will be screened for linkage to H-ESRD, including polymorphic growth factor genes causing progressive renal failure and genes involved in sodium transport and renal vascular tone. Human homologues of rodent renal failure genes identified by Dr Howard Jacob will also serve as original and informative candidate regions that are likely to be involved in human H-ESRD. If the candidate genes fail to demonstrate evidence for linkage to H-ESRD, we will perform-a systematic chromosomal survey for novel loci causing H-ESRD. The identification of hypertension-associated renal failure genes would form a genetic basis for detection of high risk individuals and development of intervention and treatment strategies for prevention of H-ESRD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL056266-04
Application #
6183931
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1997-07-01
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2003-06-30
Support Year
4
Fiscal Year
2000
Total Cost
$442,949
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
Freedman, Barry I; Cohen, Arthur H (2016) Hypertension-attributed nephropathy: what's in a name? Nat Rev Nephrol 12:27-36
Ng, Maggie C Y (2015) Genetics of Type 2 Diabetes in African Americans. Curr Diab Rep 15:74
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
Palmer, Nicholette D; Ng, Maggie C Y; Hicks, Pamela J et al. (2014) Evaluation of candidate nephropathy susceptibility genes in a genome-wide association study of African American diabetic kidney disease. PLoS One 9:e88273
Palanisamy, Amudha; Reeves-Daniel, Amber M; Freedman, Barry I (2014) The impact of APOL1, CAV1, and ABCB1 gene variants on outcomes in kidney transplantation: donor and recipient effects. Pediatr Nephrol 29:1485-92
Bailey, Jessica N Cooke; Palmer, Nicholette D; Ng, Maggie C Y et al. (2014) Analysis of coding variants identified from exome sequencing resources for association with diabetic and non-diabetic nephropathy in African Americans. Hum Genet 133:769-779
Chung, Sharon A; Brown, Elizabeth E; Williams, Adrienne H et al. (2014) Lupus nephritis susceptibility loci in women with systemic lupus erythematosus. J Am Soc Nephrol 25:2859-70
Divers, Jasmin; Palmer, Nicholette D; Lu, Lingyi et al. (2014) Gene-gene interactions in APOL1-associated nephropathy. Nephrol Dial Transplant 29:587-94
Sandy An, S; Palmer, Nicholette D; Hanley, Anthony J G et al. (2013) Genetic analysis of adiponectin variation and its association with type 2 diabetes in African Americans. Obesity (Silver Spring) 21:E721-9
Pirkle, J L; Freedman, B I (2013) Hypertension and chronic kidney disease: controversies in pathogenesis and treatment. Minerva Urol Nefrol 65:37-50

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