Environmental factors modulate the effect of the APOE genetic polymorphism on plasma lipid concentrations: Ecogenetic studies in a Mediterranean Spanish population

Abstract

To investigate APOE gene[ndash ]environment interaction effects on plasma lipid concentrations, we conducted a cross-sectional study in a Mediterranean Spanish population consisting of 396 men and 513 women aged 18 to 66 years. The frequency of the [epsi ]4 variant was 0.071 (95% confidence interval 0.059, 0.082), confirming the lower frequency of this allele in Southern Europe. In general, the carriers of the [epsi ]2 variant had lower concentrations (P [lt ] .05) of total and low-density lipoprotein cholesterol (LDL-C), carriers of the [epsi ]3 variant had intermediate concentrations, and carriers of the [epsi ]4 variant had higher concentrations (P [lt ] .05) in both sexes, even after multivariate adjustment for age, body mass index, alcohol consumption, tobacco smoking, physical activity, marital status, and education. However, when the homogeneity of allelic effects according to environmental factors was tested, significant interaction terms were found. In women, an important interaction between alcohol consumption and the APOE polymorphism in determining LDL-C concentrations was found (P [lt ] .003). LDL-C concentrations in female drinkers with the [epsi ]2 variant were significantly lower (P [lt ] .014) than in nondrinkers with the [epsi ]2 variant. Likewise, in female drinkers with the [epsi ]4 variant, LDL-C concentrations were also significantly (P [lt ] .010) lower than in nondrinkers with the [epsi ]4 variant. Moreover, in female drinkers, LDL-C concentrations did not differ between carriers of the [epsi ]4 and the [epsi ]3 variants, and in nondrinkers, LDL-C concentrations did not differ between carriers of the [epsi ]2 and the [epsi ]3 variants. We also found a statistically significant interaction effect (P [lt ] .001) between the APOE polymorphism and physical activity in determining high-density lipoprotein cholesterol concentrations in men. Our results indicate that environmental factors are important modulators of the effect of the APOE polymorphism on plasma lipid concentrations.