application) We will study the etiology of hypertension and nephropathy in the majority of the 1094 African-American patients in the African-American Study of Kidney Disease in Hypertension (AASK). The AASK study is an NIH sponsored clinical multicenter trial comparing the effect of two levels of blood pressure control and three antihypertensive regimens on progression of hypertensive nephropathy in African Americans. There is a disproportionate number of African Americans with hypertensive target organ damage, suggesting a genetic susceptibility in this population; paradoxically, few studies have been performed to evaluate such genetic predisposition to disease in this high risk population. The patients of the AASK study offer a unique opportunity to prospectively determine the genetic factors involved in hypertension and hypertensive target organ damage within a high risk and under-studied population. The proposed studies will immortalize white blood cells from patients to provide a renewable source of tissue and DNA from this unique study group, and follow two approaches in assessing the etiology of hypertension, nephropathy, and their sequelae: 1. Studies are proposed to determine whether polymorphisms in candidate genes for hypertension, renal failure, and cardiac disease, including renin-angiotensin system genes, insulin resistance (beta3-adrenergic receptor and lipoprotein lipase) genes, Liddle's syndrome (beta and gammaENaC) genes, and others are related to hypertension or renal failure, severity/rate of progression of renal disease, severity/refractoriness of hypertension, electrocardiographic left ventricular hypertrophy, cardiovascular morbidity and mortality, and overall morbidity and mortality. 2. Additional studies will employ a new technique, mapping by admixture linkage disequilibrium (MALD), which uses the linkage disequilibrium caused by recent admixture of founder populations to localize genes linked to a particular phenotype within a 5-20 centiMorgan region in a genome-wide screen. By utilizing microsatellite markers from the carefully phenotyped patients of the AASK Study it should be possible to identify regions of interest containing genes associated with hypertension, renal failure, and the outcomes described above for candidate genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK057867-05
Application #
6787786
Study Section
Special Emphasis Panel (ZDK1-GRB-5 (J3))
Program Officer
Eggers, Paul Wayne
Project Start
2000-08-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2006-07-31
Support Year
5
Fiscal Year
2004
Total Cost
$381,375
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Chen, Teresa K; Appel, Lawrence J; Grams, Morgan E et al. (2017) APOL1 Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension). Arterioscler Thromb Vasc Biol 37:1765-1769
Chen, Teresa K; Tin, Adrienne; Peralta, Carmen A et al. (2017) APOL1 Risk Variants, Incident Proteinuria, and Subsequent eGFR Decline in Blacks with Hypertension-Attributed CKD. Clin J Am Soc Nephrol 12:1771-1777
Chen, Teresa K; Choi, Michael J; Kao, W H Linda et al. (2015) Examination of Potential Modifiers of the Association of APOL1 Alleles with CKD Progression. Clin J Am Soc Nephrol 10:2128-35
Lipkowitz, Michael S; Freedman, Barry I; Langefeld, Carl D et al. (2013) Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans. Kidney Int 83:114-20
Fung, Maple M; Salem, Rany M; Lipkowitz, Michael S et al. (2012) Methylenetetrahydrofolate reductase (MTHFR) polymorphism A1298C (Glu429Ala) predicts decline in renal function over time in the African-American Study of Kidney Disease and Hypertension (AASK) Trial and Veterans Affairs Hypertension Cohort (VAHC). Nephrol Dial Transplant 27:197-205
Lee, Jason; Aziz, Hossein; Liu, Lin et al. (2011) ?(1)-adrenergic receptor polymorphisms and response to ?-blockade in the African-American study of kidney disease and hypertension (AASK). Am J Hypertens 24:694-700
Bhatnagar, Vibha; Garcia, Erin P; O'Connor, Daniel T et al. (2010) CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease. Am J Nephrol 31:95-103
Hung, Adriana M; Crawford, Dana C; Griffin, Marie R et al. (2010) CRP polymorphisms and progression of chronic kidney disease in African Americans. Clin J Am Soc Nephrol 5:24-33
Bhatnagar, Vibha; O'Connor, Daniel T; Brophy, Victoria H et al. (2009) G-protein-coupled receptor kinase 4 polymorphisms and blood pressure response to metoprolol among African Americans: sex-specificity and interactions. Am J Hypertens 22:332-8
Gainer, James V; Lipkowitz, Michael S; Yu, Chang et al. (2008) Association of a CYP4A11 variant and blood pressure in black men. J Am Soc Nephrol 19:1606-12

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