Evidence of reduced coronary artery disease risk for apolipoprotein epsilon2/3 heterozygotes

BACKGROUND: Polymorphism in the gene for apolipoprotein E (apo E) influences lipid metabolism. Relative to the epsilon3 allele, the epsilon4 allele tends to increase and the epsilon2 allele tends to decrease total and serum cholesterol, but uncertainty remains concerning an influence on the risk of coronary artery disease (CAD). It is possible that the influence of apo E alleles on CAD risk is influenced by the age of subjects studied. In this study, we examine the influence of the epsilon2 and epsilon4 alleles on the risk of CAD in relatively young subjects. METHODS: We determined the apo E genotype of 564 Caucasian CAD subjects below 50 years of age presenting with symptomatic CAD, either with or without prior myocardial infarction, and documented by angiography, and 639 similarly aged Caucasian control subjects without symptomatic CAD randomly selected from the community. RESULTS: The frequency of subjects with the epsilon2/3 genotype was significantly lower in CAD subjects than controls (6 vs. 11%, P<0.01) and, relative to epsilon3/3, the epsilon2/3 genotype was associated with a significant reduction in total and LDL-cholesterol in male and female control subjects. In contrast, there was no difference in the frequency of epsilon4/4 or epsilon4/3 genotypes in CAD cases and controls (30 vs. 26%, NS), and the latter genotypes had little influence on total or LDL-cholesterol. CONCLUSION: The results indicate a beneficial effect of the epsilon2/3 genotype not only on LDL cholesterol but in decreasing the risk of CAD in Caucasians at a young age.