The goal of this study is to understand the genetics and epidemiology of different types of early familiar coronary disease to learn how to prevent or delay early myocardial infarction and death. The first objective is to identify accurate markers of different major-gene syndromes for early coronary disease using a genetic segregation and linkage study of lipids, lipoproteins, apolipoproteins, and DNA probes in 36 large Utah pedigrees (11 previously studied pedigrees and 20 new ones). The second objective is to test for gene-environment interactions among persons of known genotype in these pedigrees based on DNA and biochemical markers. Over the past nine years, 1,336 individuals have been screened in 21 coronary-prone pedigrees in Utah, identifying five with major-genes for high cholesterol, two with major-genes for low HDL, and four with recently suggested major-genes for low apo A-I. These 11 pedigrees will be expanded to 100 persons each and restudied using the newly acquired laboratory tests for Apo B, Apo A-I, Apo E isoforms, and 7 DNA markers for Apolipoproteins and LDL receptors. Using """"""""Health Family Trees"""""""" collected yearly from parents of 12,000 Utah high school students, 200 pair of living siblings with confirmed coronary disease before age 55 will be identified and screened. Extended pedigrees will be screened for 25 pair concordant for lipid-apoprotein abnormalities and belonging to coronary-prone pedigrees of 100+ persons according to our computer-matched Utah genealogies (1.2 million persons), death certificates (240,000), and """"""""Trees"""""""" (68,000 families). Past Utah studies suggest some environmental factors such as smoking, diet, and physical activity may interact sufficiently with genetic predispositions to hasten or delay coronary disease by 20 years or more. Specific interactions will now be tested separately in pedigrees with different lipid-apoprotein coronary syndromes.
Showing the most recent 10 out of 83 publications
