Apolipoprotein E polymorphism modifies the alcohol-HDL association observed in the National Heart, Lung, and Blood Institute Family Heart Study

Background: The apolipoprotein E gene (APOE) allele ε4 is associated with an increased risk of cardiovascular disease. The presence of the ε4 allele has been associated with lower concentrations of HDL cholesterol, but it is not known whether the ε4 allele modifies the association between alcohol consumption and HDL-cholesterol concentrations. Objective: The objective of the study was to assess whether the ε4 allele modifies the association between alcohol consumption and HDL-cholesterol concentrations. Design: In a cross-sectional design, we studied 670 men and women aged 26-78 y who participated in the National Heart, Lung, and Blood Institute Family Heart Study to assess whether the ε4 allele of the gene APOE modifies the association between alcohol consumption and HDL-cholesterol concentrations. Alcohol data were self-reported, and we used multivariate, generalized estimating equations to assess interactions. Results: In a model with adjustment for age, sex, body mass index, smoking, exercise, waist-hip ratio, TV viewing, and study site, there was a significant effect of the interaction between the ε4 allele and alcohol consumption on HDL cholesterol (P = 0.0001). In the absence of the ε4 allele, multivariate adjusted means of HDL were 1.24, 1.36, and 1.54 mmol/L among subjects who never drank and those who currently drink 0.1-12 and >12 g alcohol/d, respectively; in the presence of the ε4 allele, the corresponding values were 1.19, 1.27, and 1.25 mmol/L. Conclusion: Our data show a significant effect of the interaction between the ε4 allele and alcohol consumption on HDL. The increase in HDL associated with alcohol appears to be stronger in subjects without the ε4 allele than in those with the ε4 allele.