Our long term research goal is to identify genetic and environmental causes of atherosclerotic coronary artery disease (CAD) in African Americans (AA) to enable us to design, test and implement preventive and therapeutic strategies. The specific goal of this grant is to develop a set of AA family based clinical material that will allow us to delineate the molecular genetic etiologies of CAD and lipid abnormalities. Our general approach will be to systematically collect physiologic and genetic information on an AA family data base and analyze it with state of the art statistical genetic techniques. We will meet this goal by carrying out the following specific aims: 1. Identify through angiography at least 2000 African Americans with proven CAD. 2. Select from these potential probands 250 families with at least 4 first degree relatives living within 100 miles of our study site. 3. Determine the population distribution of the major physiological risk factors for CAD in these 1250 AAs: office and 24 hr ambulatory blood pressure, echocardiographic LVM, and ultrafast cardiac CT for the presence of calcium in the coronary arteries. 4. Determine genotypes for certain blood groups, red cell enzymes, and serum proteins-which reflect Caucasian and African admixture, and for known CAD genetic markers for CAD and lipid abnormalities, including ultracentrifuge lipoprotein analysis, Lp(a) and ApoE isoforms. 5. Compare the population distribution of white probands with proven CAD and their family members recruited at Cedars-Sinai with a similar protocol funded by another NIH grant. 6. Utilize state of the art genetic analytic methods to delineate molecular genetic etiologies of atherosclerosis and lipid abnormalities in these affected AA families. 7. To establish chromosomal regions of interest for further studies using a comprehensive genomic approach . These studies will markedly increase our knowledge of the known factors determining CAD in AA and should lead to new prevention and treatment methods.
