The goal of this project is to contribute to our understanding of the genetic basis of hypertension (HTN) in? African-Americans (AA). Hypertension disproportionately affects AA and its complications contribute? immensely to health disparity experienced by AA through increased morbidity and mortality from stroke,? heart failure, kidney failure and coronary heart disease. It is now accepted that HTN results from a complex? interplay between genetic and environmental factors. However, the environmental risk factors, which include? lifestyle, dietary and psycho-social factors, have been better characterized than the genetic ones. Linkage? and candidate gene studies have so far provided limited success across studies and population groups.? Building on the success of a previously funded study of the genetic epidemiology of AA families in the? Washington DC metropolitan area, we propose to enroll a population sample of HTN cases and unaffected? controls, genotype a panel of ancestry informative markers (AIM) in the sample and utilize the admixture? mapping approach to identify genomic regions associated with HTN. During a clinical examination, we will? collect demographic information and measure blood pressure, anthropometry and body composition. Blood? will be drawn for biochemical assays (sodium, potassium, creatinine, urea, glucose) and several other? molecular phenotypes (including cortisol, endothelin-1, C-reactive protein, insulin, leptin). Genomic DNA will? be extracted. A published panel of 3,011 well-characterized AIM single nucleotide polymorphisms (SNPs)? will be genotyped in 500 HTN cases and 500 controls. Locus-genome statistics (for cases only) and casecontrol? statistics will be calculated and used to identify ancestral genomic regions that have susceptibility? genes for HTN. The identified regions will be followed up with a SNP fine map at a density of approximately 10 kb to? further refine the regions and move closer to the genes that need further study by resequencing, mutation? detection, replication and functional studies. Taking advantage of the unique historic experience of AA and a? new genetic strategy (admixture mapping), this project has the potential to provide useful insights into how? genetic inheritance predisposes to hypertension and to contribute to our understanding of how to develop? better strategies for hypertension prevention, treatment and control.?
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