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Apolipoprotein E polymorphism modifies the alcohol-HDL association observed in the National Heart, Lung, and Blood Institute Family Heart Study^1,2,3

¹ From the Section of Preventive Medicine & Epidemiology, Evans Department of Medicine (LD and RCE), and the Department of Neurology (RHM), Boston University School of Medicine, Boston, and the Division of Epidemiology (JSP and DKA) and the Department of Laboratory Medicine and Pathology (JHE), University of Minnesota, Minneapolis

Background:The apolipoprotein E gene (APOE) allele 4 is associated with an increased risk of cardiovascular disease. The presence of the 4 allele has been associated with lower concentrations of HDL cholesterol, but it is not known whether the 4 allele modifies the association between alcohol consumption and HDL-cholesterol concentrations.

Objective:The objective of the study was to assess whether the 4 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 4 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 4 allele and alcohol consumption on HDL cholesterol (P = 0.0001). In the absence of the 4 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 4 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 4 allele and alcohol consumption on HDL. The increase in HDL associated with alcohol appears to be stronger in subjects without the 4 allele than in those with the 4 allele.

Key Words: Apolipoprotein E • alcohol consumption • interaction • HDL cholesterol • lipids

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