The goal of this study is to define the genetics of coronary artery disease and coronary collateralization in African Americans and whites. We will study patients from a German population, and from the Milwaukee area. The German population (Caucasian) consists of affected siblings with coronary artery disease, and non-affected siblings to serve as a control population for different allelic frequencies. These patients will be genotyped and phenotyped according to the presence of coronary disease and coronary collateralization. The results from this research could initiate new therapies based on supplementing specific gene therapies or growth factors to correct for genetic deficiencies. From this analysis we will affirm initial linkage of specific chromosomal loci with the phenotypes of coronary disease or degree of collateralization. After completing the study of the German subjects we will study a heterogeneous population in the Milwaukee area with at least one totally occluded major coronary artery. By design this population will be selected to include 600 women, 600 men and the ethnicity will be 50% African American and 50% Caucasian. Cases ()n=300) will be those with the highest grade of collateral development (Rentrop class 3) and Controls (n=300) will be those with no collateralization (Rentrop class 0). We will also collect 300 each in Rentrop Class 1 and 2 to test for genetic effects on the quantitative score. Phenotyping will include insulin sensitivity and echocardiographic left ventricular mass. This case/control design will test specific candidate genes that were elucidated in the first phase of the study (German sibling study). In addition other candidate regions will be examined on the basis of 1) growth factors found to be expressed in Project 1; 2) genotype/risk factor associations seen in African American families with CAD (from our genotype/risk factor associations seen in African American families with CAD (from our current studies); and 3) the human homologous regions to rat genes mapped in Project 3. Collectively, we believe our study will provide one of the most complete analyses in revealing insight into the genetic basis of coronary artery disease and growth of the coronary collateral circulation.
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