The objective of the proposed study is to determine the contribution of polymorphic variation in ten candidate genes involved in lipid metabolism (A-IV, B, D, E, H, APO(a), LDL receptor, hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein) in determining quantitative lipoprotein-lipid levels and cardiovascular risk factors in Anglo and Hispanic populations of the San Luis Valley in southern Colorado. Genetic variation in the gene products of A-IV, E, H, and APO(a) will be determined by IEF and SDS/immunoblotting; gene variation at the APOB, D, LDL receptor, hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein will be assayed by polymerase chain reaction protocols and using cloned cDNA probes for RFLPs analyses. Direct haplotype analysis of individuals will employ a strategy using RFLP analysis combined with the use of allele specific oligonucleotides. Quantitative levels of apolipoprotein B, E, H and APO (a) will be determined by immunological techniques. These data and prior data on levels of triglycerides, total cholesterol, HDL-, LDL- and HDL subfraction cholesterol will be used in the quantitative genetic analysis. Estimates of the effect of alleles at each of the genetic loci on the quantitative apolipoprotein and lipoprotein levels will employ the measured genotype approach. The effort of multisite haplotypes for RFLPs at various loci will be estimated using the same methods. For common alleles in each system the interaction of alleles at independent genetic loci in determining quantitative variables will be estimated. Dietary information from the San Luis Valley population will be used to estimate cholesterol intake identified. Allelic effects will be estimated in these groups to gain insight into the effect of dietary cholesterol intake of the estimated allelic effects.
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