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

To investigate APOE gene-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 epsilon4 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 epsilon2 variant had lower concentrations (P <.05) of total and low-density lipoprotein cholesterol (LDL-C), carriers of the <epsilon>3 variant had intermediate concentrations, and carriers of the epsilon4 variant had higher concentrations (P <.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 <.003). LDL-G concentrations in female drinkers with the epsilon2 variant were significantly lower (P <.014) than in nondrinkers with the <epsilon>2 variant. Likewise, in female drinkers with the epsilon4 variant, LDL-C concentrations were also significantly (P <.010) lower than in nondrinkers with the <epsilon>4 variant. Moreover, in female drinkers, LDL-G concentrations did not differ between carriers of the epsilon4 and the epsilon3 variants, and in nondrinkers, LDL-C concentrations did not differ between carriers of the epsilon2 and the e3 variants. We also found a statistically significant interaction effect (P <.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. Copyright (C) 2001 by W.B. Saunders Company.