Epidemiological studies have established a positive correlation in humans between coronary artery disease and the serum levels of low density lipoprotein cholesterol, whereas atherosclerosis appears to bear a negative relationship with serum concentrations of high density lipoprotein cholesterol. More recently, some investigators showed that serum apolipoproteins are probably better discriminative factors than serum lipids to distinguish coronary artery disease patients from normal controls. Serum apolipoprotein levels can be affected by diets, alcohol consumption, obesity and exercise. However, the extents of these effects are often found to be variable among human or animal subjects. One possible reason for these observations may be due to genetic variance of serum apolipoproteins. We plan to utilize the Indiana University Twin Panel to test for this possibility.
The specific aims for this proposal are: (1) to develop ELISA methods for the quantification of human plasma apolipoproteins i.e. apo AI, AII, AIV and E in total plasma and in the HDL fraction; (2) to determine the genetic heritability of human apolipoproteins; and (3) to partial out the effects of ethanol consumption, exercise and obesity on apolipoproteins. Our studies in the rat showed that ethanol feeding increased serum HDL but, HDL particles of the ethanol-fed rats were deficient in apo E. In the future, we plan to carry out parallel studies in human alcoholics to examine whether HDL particles in alcoholic subjects are deficient in apo E as in rats fed ethanol chronically, and to study the genetic heritability of the responsiveness to the alcohol effect on apolipoproteins.
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