Phenotypic Effects of Apolipoprotein Structural Variation on Lipid Profiles Contribution of Apolipoprotein E Phenotype to Prediction of Total Cholesterol, Apolipoprotein B, and Low Density Lipoprotein Cholesterol in the Healthy Women Study

The apolipoprotein (apo) E structural locus has been shown to Influence concentrations of total cholesterol, apo B, and low density lipoprotein (LDL) cholesterol In population studies. Apo E has six phenotypes resulting from three common alleles at this locus. In the present study, we have typed 473 healthy white women for apo E. At baseline In 1984, all women were premenopausal. To date, 109 of these women have become postmenopausal and are not on hormone therapy. Statistical analyses were done on both preand postmenopausal groups to assess the influence of menopausal status In combination wtth the apo E locus on Mpld profile. Nine lipoprotein llplds and apollpoprotelns were categorized by three apo E phenotypes: apo E3-2, apo E3-3, and apo E4-3. These were compared In analysis of variance. At baseline, the apo E3-2 phenotype showed the lowest average concentrations of total cholesterol (170 mg/dl), apo B (80 mg/dl), and LDL cholesterol (91 mg/dl), while the apo E4-3 phenotype demonstrated the highest average concentrations of total cholesterol (192 mg/dl), apo B (104 mg/dl), and LDL cholesterol (116 mg/dl) (ps0.0004). Apo E3-3 homozygotes were Intermediate on all three quantitative variables. The postmenopausal subset showed the same trends by phenotype, with overall Increases in total cholesterol, apo B, LDL cholesterol, and trlglycerldes, regardless of phenotype. Women who remained premenopausal generally showed smaller Increases in these same measures. Our results suggest that, on average, the lower lipoprotein values for the apo E3-2 phenotype are maintained through early menopause despite a worsening of llpid profiles for all women as they age. There did not appear to be a marked effect of apo E phenotype on change In lipoprotein llplds and apolipoprotelns that might reflect an Interaction between this locus and hormonal status. In addition, the effects of several environmental determinants of total cholesterol, apo B, and LDL cholesterol, along with apo E, were assessed by multivariate regression analysis. (Arteriosclerosis 10:379-385, May/June 1990)