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

To investigate APOE gene-environment interaction effects on plasma lipid co ncentrations, we conducted a cross-sectional study in a Mediterranean. Span ish 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, eve n after multivariate adjustment for age, body mass index, alcohol consumpti on, tobacco smoking, physical activity, marital status, and education. Howe ver, when the homogeneity of allelic effects according to environmental fac tors was tested, significant interaction terms were found. In women, an imp ortant 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 signific antly (P <.010) lower than in nondrinkers with the <epsilon>4 variant. More over, in female drinkers, LDL-G concentrations did not differ between carri ers of the epsilon4 and the epsilon3 variants, and in nondrinkers, LDL-C co ncentrations did not differ between carriers of the epsilon2 and the e3 var iants. We also found a statistically significant interaction effect (P <.00 1) 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 A POE polymorphism on plasma lipid concentrations. Copyright (C) 2001 by W.B. Saunders Company.