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.
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