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To determine the role of genetic factors in predicting resistance and susceptibility to coronary artery disease.
Coronary artery disease appears to be a consequence of the interaction between an individual's genotype and exposure to environmental factors. Genetic information has the potential to contribute to the identification of families and individuals with a biological predisposition for developing coronary artery disease. Although numerous studies have suggested the possibility of a link between polymorphic genetic variation and coronary heart disease, it has not been possible to use any single genetic locus or combination of loci to establish a person's risk except for the case of familial hypercholesterolemia.
Apolipoproteins play a critical role in regulating cellular uptake of lipoproteins by specific receptors, regulating the activities of lipoprotein lipase and lecithin-cholesterol acyl transferase, and in the indirect regulation of the intracellular enzymes, acyl-cholesterol acyl transferase and HMG Co-A reductase. This study provided insight into the role of environmental and genetic effects on phenotypic variation of the individual components of the molecules of lipid metabolism as well as on the relationships between components.
Previous studies conducted under this grant include: the relationship between quantitative levels of apo A-I and coronary artery disease as defined by coronary angiography; the effects of exercise, alcohol, obesity, and pregnancy on apo A-I levels; the relationship between apo A-I and HDL levels in children and the mode of inheritance of apo A-I levels in pedigrees in the Rochester, Minnesota community; and characterization of the antigenic structure of apolipoproteins in coronary artery disease.
Subjects for the study were drawn from the Rochester Family Heart Study which initiated recruitment for the family study in January 1985. In 31 months of recruitment, 443 households were contacted and 300 agreed to participate. In August 1987 all individuals identified by these households had completed their clinic visits providing 1,999 physical exams. The 300 households yielded 276 three and four generation pedigrees with 593 parents, 598 grandparents, 14 great-grandparents, and 854 children. Disease information was obtained from medical records for an additional 400 grandparents. In 1988 an additional 2,100 individual members of 300 families were surveyed.
Medical records and death certificates were reviewed to evaluate coronary artery disease endpoints in all adults members of the pedigrees. Clinical data collected included: a history of symptoms of coronary artery disease, arteriosclerosis obliterans, cerebrovascular disease or surgery for these diseases; smoking; medication; history of genetic relationships. Measurements were made of cholesterol, triglycerides, HDL and LDL cholesterol, apo A-I, apo A-II, apo E, apo C-III, apo C-II, apo B, apo Lp(a), LDL apo B, HDL apo E, and DNA extraction. Lipid, lipoprotein, and apolipoprotein phenotypes and the restriction fragment length polymorphisms (RFLP) were measured in candidate genes for coronary artery disease. Genetic and phenotype analyses were conducted at the University of Michigan. The RFLP and apolipoprotein isotyping analyses were conducted at the University of Pittsburgh. RFLP analysis and LDL receptor and A-I gene analysis were conducted at Charing Cross Medical Center in London, England.
Observational Model: Natural History
National Heart, Lung, and Blood Institute (NHLBI)
Published on BioPortfolio: 2014-08-27T03:58:00-0400
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Cardiovascular disease (CVD)
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