Background: The prevalence of cardiovascular risk factors and atherosclerosis vary between ethnic groups. We examined the apolipoprotein E (ApoE) polymorphism, its association with lipid traits and atherosclerosis, and its influence on ethnic variations on lipid traits.
Methods: In a randomly sampled cross-sectional study of 985 South Asian, Chinese, and European Canadians, three common isoforms of ApoE (E2, E3 and E4), plasma lipid concentrations and atherosclerosis of the carotid artery were measured.
Results: The E2, E3 and E4 allele frequencies were 5.7%, 84.0%, and 10.2%, respectively, and differed significantly between ethnic groups. There was a strong, stepwise association between ApoE and each plasma lipid trait, except triglycerides. The E4 genotype was associated with higher low-density lipoprotein cholesterol (p for trend<0.001), ApoB (p<0.001), ApoB/ApoA ratio (p<0.001) and lipoprotein (a) (p<0.001), and lower ApoA (p<0.001) and high-density lipoprotein cholesterol (HDL-C) (p=0.005). A similar pattern of effects was observed across all ethnic groups. Ethnicity accounted for modest variation in ApoA, ApoB/ApoA ratio and HDL-C (4.2-5.0%), whereas ApoE isoforms explained only a small proportion of variability (0.3-1.4%). Dietary and lifestyle factors accounted for modest variation in several traits including HDL-C (5.6% and 5.0%, respectively). Carotid atherosclerosis was lower among individuals with E2 isoform in keeping with the effect of E2 on lipid levels.
Conclusions: The ApoE isoform is associated with plasma lipoproteins in all ethnic groups, yet explains only a small proportion of the inter-ethnic variation for most plasma lipoproteins. Additional genetic variants and/or health behaviors likely contribute to ethnic variations in plasma lipid traits.