Abstract

PURPOSE: To evaluate the impact of apolipoprotein E (apoE) genotypes on lipoprotein measurements relative to that of other known cardiovascular risk factors 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 Heart Study, and then tested the association between the three common apoE genotypes ( ϵ2ϵ3, ϵ3ϵ3, and ϵ3ϵ4) and lipoprotein traits using the measured genotype approach to account for residual familial correlations. RESULTS: Allele frequencies in this population for ϵ2, ϵ3, and ϵ4 were 3.5%, 89.6%, and 6.9%, respectively. As expected, adjusted apoE concentrations were highest in those with ϵ2ϵ3, intermediate in those with ϵ3ϵ3, and lowest in those with ϵ3ϵ4. The concentrations of total cholesterol, LDL-C and apoB were lowest in those with ϵ2ϵ3, intermediate in those with ϵ3ϵ3, and highest in those with ϵ3ϵ4. There was no significant effect of apoE genotypes on triglycerides, HDL-C, or apoAI levels. Compared to subjects with ϵ3ϵ4, subjects with ϵ2ϵ3 had relatively less apoE in LDL and HDL 1, and relatively more in HDL 2 and HDL 3 size fractions. The effect of apoE genotypes was significantly greater on apoB in women than in men sex × 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, proportion of phenotypic variation in concentrations of LDL-C, apoB, and apoE, and distributions of apoE among lipoproteins in this population; these genotypes have a greater effect on apoB levels in women than in men.

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