Several of the common chronic diseases, including coronary heart disease and diabetes, are associated with altered lipid metabolism. This research will investigate the genetics and epidemiology of fasting and postprandial lipid, lipoprotein, and apolipoprotein levels. Previous studies have established that polygenetic variability is contributing to fasting measures of lipid metabolism. These studies do not yield information about the effects of specific genes. Estimating the effects of specific candidate genes will facilitate investigating the interaction between genetic and environmental factors. We will first determine the effects of the apolipoprotein B and E genes on fasting levels of lipids (total cholesterol and trigycerides), lipoproteins (LDL-cholesterol, HDL-cholesterol, HDL2- cholesterol, HDL3-cholesterol), and apolipoproteins (apo A-I B, C- III, and E). Genetic variability will be directly assessed by DNA restriction site variability in the apolipoprotein B gene and by measuring the apolipoprotein E polymorphism. These loci have been chosen because of their likely interaction with dietary factors. These analyses will be carried out on a sample of 75 nuclear families from Nancy France. These families have already been ascertained, blood samples obtained and extensive data collected so that this proposed research can be initiated with a considerable savings of time and money. Data collected from families will enable us to partition the effects of the apolipoprotein B and E genes from the overall polygenetic and phenotypic variance of the measured lipids, lipoproteins, and apolipoproteins. Results and experience obtained from these studies will be applied to investigations of the effects of these loci on the response to a standard meal. Both fasting and postprandial lipids, lipoproteins, an apolipoproteins will be obtained on a sample of 100 unrelated Mexican-Americans from Laredo, Texas. We will investigate the distribution and sources of variability contributing to postprandial lipid levels. We will determined the the effects of factors such as the apolipoprotein E and B genes, disease status, age, and their interactions on fasting and postprandial lipid metabolism. This FIRST research proposal is part of the principal investigator's developing research program on the interaction between genetic and environmental factors contributing to the constellation of diseases prevalent among Mexican-Americans. This research will yield a better understanding of the interaction between genetic predisposition and diet in contributing to interindividual variability in lipid- related measures.
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