PURPOSE: To evaluate the impact of apolipoprotein E (apoE) genotypes on lip
oprotein measurements relative to that of other known cardiovascular risk f
actors in participants of a large population-based family study.
METHODS: We measured concentrations of apoE, the major constituents of HDL
(cholesterol, apoAI), LDL-C (cholesterol and apoB), and fraction of apoE in
lipoprotein size classes in 859 participants of the San Antonio Family Hea
rt Study, and then tested the association between the three common apoE gen
otypes (epsilon2 epsilon3, epsilon3 epsilon3, and epsilon3 epsilon4) and li
poprotein traits using the measured genotype approach to account for residu
al familial correlations.
RESULTS: Allele frequencies in this population for epsilon2, epsilon3, and
epsilon4 were 3.5%, 89.6%, and 6.9%, respectively. As expected, adjust-ed a
poE concentrations were highest in those with epsilon2 epsilon3, intermedia
te in those with epsilon3 epsilon3, and lowest in those with epsilon3 epsil
on4. The concentrations of total cholesterol, LDL-C and apoB were lowest in
those with epsilon2 epsilon3, intermediate in those with epsilon3 epsilon3
, and highest in those with epsilon3 epsilon4. There was no significant eff
ect of apoE genotypes on triglycerides, HDLC, or apoAI levels. Compared to
subjects with epsilon3 epsilon4, subjects With epsilon2 epsilon3 had relati
vely less apoE in LDL and HDL1, and relatively more in HDL2 and HDL3 size f
ractions. The effect of apoE genotypes was significantly greater on apoB in
women than in men (sex x apoE interaction p-value = 0.02). ApoE genotypes
accounted for 4.5%, 12.3%, and 4.7% of the total genetic variation in apoB,
apoE, and LDL-C, respectively.
CONCLUSION: ApoE genotypes account for a modest, albeit significant, propor
tion of phenotypic variation in concentrations of LDL-C, apoB, and apoE, an
d distributions of apoE among lipoproteins in this population; these genoty
pes have a greater effect on apoB levels in women than in men. (C) 2000 Els
evier Science Inc. All rights reserved.