Obesity and Alcohol Modulate the Effect of Apolipoprotein E Polymorphism on Lipids and Insulin

Objective: To assess the interaction between apolipoprotein (apo) E polymorphism, alcohol consumption, and BMI on insulin, lipid, and lipoprotein levels in men. Research Methods and Procedures: Cross‐sectional study of 266 healthy men without hypolipidemic or antidiabetic drug treatment. BMI, apo E polymorphisms, insulin, and lipid and lipoprotein levels were assessed. Alcohol consumption was assessed by questionnaire. ?2/?4 carriers were excluded from the analysis. Results: On bivariate analysis, ?2 carriers had lower levels of total and low‐density lipoprotein cholesterol and higher levels of apo E and lipoparticle B:E than ?3 carriers, the opposite being found for ?4 carriers compared with ?3 carriers; ?4 carriers also had significantly higher insulin levels. On multivariate analysis, significant interactions (p < 0.04) between apo E alleles and increased BMI were found for total and low‐density lipoprotein cholesterol and insulin levels, the increase in those parameters with BMI being stronger among ?4 carriers than among ?3 or ?2 carriers. Significant interactions (p < 0.02) between apo E alleles and alcohol consumption were also found for apo B levels, which increased in ?2 carriers but remained relatively stable in ?3 and tended to decrease in ?4 carriers. Discussion: These data suggest that effects of apo E alleles on lipids and insulin levels are partly dependent on environmental variables such as BMI and alcohol intake. These findings highlight the importance of gene × environment interactions on the deleterious effect of obesity on cardiovascular risk factors.