Identification of genetic risk factors has the potential to improve the diagnosis, treatment, and importantly, primary prevention of heart failure. However, the biological complexity of heart failure suggests that simple epidemiological association studies will not be sufficient to tease out the relevant genetic events without hypothesis-driven physiological studies in genetically or phenotypically similar patient cohorts. The Core's main purpose will be to coordinate and integrate genotype/phenotype catalogues among the Projects, such that the results can be more quickly translated to the clinical setting, collaborations can proceed more quickly, and quality control and database construction are performed at a central point for maximum effectiveness. A central focus of the Core is the Cincinnati Heart Failure Study, initiated in 1995 as a prospective consecutive study of patients enrolled for evaluation and treatment of congestive heart failure at the University of Cincinnati Heart Failure and Transplantation Clinic. This study has allowed us to identify polymorphisms of adrenergic receptors and other signaling genes that predict susceptibility to, or that modify the course of, heart failure. Recently, we established a collaboration with Drs. Greg Freeman and David Murray at the University of Texas Health Science Center San Antonio, San Antonio to add the San Antonio Heart Study to our investigations. This cohort of heart failure patients provides us access to subjects of Latin heritage, and will therefore help us to establish the appropriate racial balance in our genetic studies. In support of haplotype discovery and identification in Projects 1-3 of the Cincinnati SCCOR, the Heart Failure Genomics Core will recruit into, and perform genetic fingerprinting and phenotyping of, multi-ethnic heart failure cohorts. The Core will perform genetic analyse of independent heart failure cohorts for confirmation of associations, leading to detailed invasive and noninvasive comparative analyses of specific haplotypes, as described in individual Projects, that will define the physiological consequences of observe gene variations. Towards this end the Core will provide the following services: 1. Identify and recruit heart failure patients and non-affected controls into the Cincinnati/San Antonio Heart Study and perform initial cardiac phenotyping and longitudinal phenotypic assessments of Study patients. 2. Acquire, process, and store DNA from Study subjects and identify genetic variations in heart failure-related genes. 3. Establish and maintain the DNA-Phenotype Database.
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