Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations.

To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, we have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of postprandial response in plasma was monitored over 8 h by triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B-100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was determined by DNA amplification and digestion. The frequency of the apo E alleles and their effects on fasting lipid levels in this sample were similar to those reported elsewhere. Postprandial plasma retinyl palmitate response to a high-fat meal with vitamin A was significantly different among apo E genotypes, with delayed clearance in individuals with an epsilon 2 allele, compared with epsilon 3/3 and epsilon 3/4 individuals. In the sample of 397 Caucasians, average retinyl palmitate response was 1,489 micrograms/dl in epsilon 2/3 individuals, compared with 1,037 micrograms/dl in epsilon 3/3 individuals and 1,108 micrograms/dl in epsilon 3/4 individuals. The apo E polymorphism accounted for 7.1% of the interindividual variation in postprandial retinyl palmitate response, a contribution proportionally greater than its well-known effect on fasting LDL-cholesterol. However, despite this effect on postprandial retinyl palmitate, the profile of postprandial triglyceride response was not significantly different among apo E genotypes. The profile of postprandial response was consistent between the sample of Caucasians and a smaller sample of black subjects. While these data indicate that the removal of remnant particles from circulation is delayed in subjects with the epsilon 2/3 genotype, there is no reported evidence that the epsilon 2 allele predisposes to coronary artery disease (CAD). The results of this study provide not only a reliable estimate of the magnitude of the effect of the apo E polymorphism on various measurements commonly used to characterize postprandial lipemia, but also provide mechanistic insight into the effects of the apo E gene polymorphism on postprandial lipemia and CAD.

[1]  R. Mahley,et al.  Apoprotein (E--A-II) complex of human plasma lipoproteins. II. Receptor binding activity of a high density lipoprotein subfraction modulated by the apo(E--A-II) complex. , 1978, The Journal of biological chemistry.

[2]  C. Williams,et al.  Postprandial Lipoprotein Metabolism , 1993, Nutrition Research Reviews.

[3]  S. Grundy,et al.  Increased Low Density Lipoprotein Production Associated with Obesity , 1983, Arteriosclerosis.

[4]  J. Albers,et al.  Isolation and Characterization of Human Plasma Lipid Transfer Proteins , 1984, Arteriosclerosis.

[5]  C. Ehnholm,et al.  Intestinal cholesterol absorption efficiency in man is related to apoprotein E phenotype. , 1987, The Journal of clinical investigation.

[6]  L. Krimbou,et al.  İnsan HDL'si biyogenezine yeni bakışlar , 1990 .

[7]  A. Cooper,et al.  Regulation of apoprotein synthesis and secretion in the human hepatoma Hep G2. The effect of exogenous lipoprotein. , 1988, The Journal of biological chemistry.

[8]  R. Gregg,et al.  Increased prevalence of apolipoprotein E4 in type V hyperlipoproteinemia. , 1982, The Journal of clinical investigation.

[9]  Plasma triglyceride and coronary heart disease. , 1991 .

[10]  B. Paulweber,et al.  Heterozygous lipoprotein lipase deficiency due to a missense mutation as the cause of impaired triglyceride tolerance with multiple lipoprotein abnormalities. , 1993, The Journal of clinical investigation.

[11]  T. Lohman,et al.  Anthropometric Standardization Reference Manual , 1988 .

[12]  M. Brown,et al.  Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. , 1983, Annual review of biochemistry.

[13]  Michael H. Kutner.  Applied Linear Statistical Models , 1974 .

[14]  D. F. Morrison,et al.  Multivariate Statistical Methods , 1968 .

[15]  W. A. Bradley,et al.  Distinct murine macrophage receptor pathway for human triglyceride-rich lipoproteins. , 1988, The Journal of clinical investigation.