BACKGROUND:

Preliminary work for this project was carried out as part of the Johns Hopkins Coronary Artery Disease study (R01-HL-34791) which provided extensive data on families ascertained through equal numbers of white male and female probands undergoing elective angiography.

DESIGN NARRATIVE:

The study, a subproject within an Arteriosclerosis SCOR, had three components. In Component 1, the group of 203 probands under study R01HL34791 was expanded with an additional 50 black patients undergoing angiography, meeting identical criteria. In Component 2, segregation analysis was carried out on lipoproteins, apolipoproteins, and selected non-traditional risk factors on families of all probands and the etiologic heterogeneity among different groups of families was tested. In Component 3, linkage was tested between putative Mendelian loci defined in Component 2 and markers in and around candidate loci involved in lipid metabolism. Preliminary results provided evidence of Mendelian control for apolipoprotein A1 and B, and the candidate loci examined included apo B, lipoprotein lipase, and the A1-CIII-A4 gene cluster. The major hypothesis was that these apolipoprotein levels and other non-traditional risk factors might be under genetic control. Genetic analysis of these risk factors was used to direct molecular studies to identify specific mutations.