Alcohol drinking determines the effect of the APOE locus on LDL-cholesterol concentrations in men: the Framingham Offspring Study

Background: The effect of alcohol drinking on LDL-cholesterol concentration s is unclear. The reported variability may be due to interactions between g enetic factors and alcohol intake. Objective: The purpose of the study was to examine whether variation at the apolipoprotein E gene (APOE) locus modulates the association between alcoh ol drinking and LDL cholesterol. Design: We used a cross-sectional design in a healthy population-based samp le of 1014 men and 1133 women from the Framingham Offspring Study. Results: In male nondrinkers (n = 197), LDL cholesterol was not significant ly different across APOE allele groups [APOE*E2 (E2), APOE*E3 (E3), and APO E*E4 (E4)]. However, in male drinkers (n = 817), differences were observed (P < 0.001); those with the E2 allele had the lowest concentrations. LDL ch olesterol in men with the E2 allele was significantly lower in drinkers tha n in nondrinkers but was significantly higher in drinkers than in nondrinke rs in men with the E4 allele. This APOE-alcohol interaction remained signif icant (P < 0.001) after age, body mass index, smoking status, and fat and e nergy intakes were controlled for. In women, the expected effect of APOE al leles on LDL cholesterol occurred in both drinkers (n = 791; P < 0.001) and nondrinkers (n = 342; P < 0.001). Multiple linear regression models showed a negative association (P < 0.05) between alcohol and LDL cholesterol in m en with the E2 allele but a positive association in men with the E4 allele. No significant associations were observed in men or women with the E3 alle le. Conclusion: In men, the effects of alcohol intake on LDL cholesterol are mo dulated in part by variability at the APOE locus.