This is a continuation of our efforts to determine the role of genetic factors in predicting resistance and susceptibility to coronary artery disease (CAD). We will utilize assays of candidate genes and their products that have been recently developed to characterize an individual's genotype. These assays will provide measurements of the LDL receptor function, qualitative and quantitative phenotypes of seven apolipoproteins and restriction fragment length polymorphisms for the candidate genes that code for these apolipoproteins. We will utilize the biochemical and clinical measurements of hyperlipidemia and CAD to characterize the cardiovascular health of each individual. The proposed studies will combine information about the genotype, gene products, intermediate phenotypes of lipid metabolism, and the CAD endpoint to establish the genetic factors that can be used to predict CAD. We expect that a fraction of the information about an individuals risk to CAD provided by DNA and gene product polymorphisms will be expressed through the intermediate phenotypes of lipid metabolism and a fraction will act independently in a pleiotropic fashion to predict CAD.
In Aim 1 we will collect 300 three-generation families selected to represent the Rochester, Minnesota population. We require these additional date on families to obtain adequate numbers of individuals at risk to establish which of the measurements of the genetic loci and intermediate phenotypes of lipid metabolism predict risk of CAD.
In Aim 2 we will determine which genotypes and phenotypes characterized in Aim 1 can be used to discriminate between seven different clinical types of CAD.
In Aim 3 we will determine whether or not any of the genotypes and/or phenotypes identified in Aim 1 can be used to predict the response of hyperlipidemia to drug therapy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL024489-09
Application #
3337706
Study Section
Epidemiology and Disease Control Subcommittee 3 (EDC)
Project Start
1983-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
9
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Rebbeck, T R; Turner, S T; Sing, C F (1993) Sodium-lithium countertransport genotype and the probability of hypertension in adults. Hypertension 22:560-8
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Sing, C F; Haviland, M B; Zerba, K E et al. (1992) Application of cladistics to the analysis of genotype-phenotype relationships. Eur J Epidemiol 8 Suppl 1:3-9
Reilly, S L; Ferrell, R E; Kottke, B A et al. (1992) The gender-specific apolipoprotein E genotype influence on the distribution of plasma lipids and apolipoproteins in the population of Rochester, Minnesota. II. Regression relationships with concomitants. Am J Hum Genet 51:1311-24
Mailly, F; Moll, P; Kottke, B A et al. (1992) Estimation of the frequency of isoform-genotype discrepancies at the apolipoprotein E locus in heterozygotes for the isoforms. Genet Epidemiol 9:239-48
Turner, S T; Rebbeck, T R; Sing, C F (1992) Sodium-lithium countertransport and probability of hypertension in Caucasians 47 to 89 years old. Hypertension 20:841-50

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