To test whether plasma lipoprotein levels and low density lipoprotein (LDL) particle size are modulated by an interaction between habitual saturated fat intake and apolipoprotein E (APOE) genotype, we studied 420 randomly selected free-living Costa Ricans. The APOE allele frequencies were 0.03 for APOE2, 0.91 for APOE3, and 0.06 for APOE4. The median saturated fat intake, 11% of energy, was used to divide the population into two groups, LOW-SAT (mean intake 8.6% energy) represents those below median intake, and HIGH-SAT (mean intake 13.5%) represents those above median intake. Significant interactions between APOE genotype and diet were found for VLDL (P = 0.03) and HDL cholesterol (P = 0.02). Higher saturated fat intake was associated with higher VLDL cholesterol (+29%) and lower HDL cholesterol (-22%) in APOE2 carriers, while the opposite association was observed in APOE4 carriers (-31% for VLDL cholesterol and +10% for HDL cholesterol). Higher saturated fat intake was associated with smaller LDL particles (-2%, P < 0.05) in APOE2 carriers, and larger LDL particles (+2%, P < 0.05) in APOE4 carriers, but the gene-diet interaction was not statistically significant (P = 0.09). Higher saturated fat intake was associated with higher LDL cholesterol in all genotypes (mean +/- SEM, LOW-SAT 2.61 +/- 0.05 vs. HIGH-SAT 2.84 +/- 0.05 mmol/L, P = 0.009). These data suggest that the APOE2 allele could modulate the effect of habitual saturated fat on VLDL cholesterol and HDL cholesterol in a population with an average habitual total fat intake of less than 30%.
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