Meta-analysis suggests there are roughly linear relationships for apolipoprotein E genotype with lipid levels and degree of coronary risk, according to an article in the September 19 issue of the Journal of the American Medical Association.

Some previous studies had found associations between certain apoE genotypes and lipid levels and coronary risk, but many of those studies were small in size and could have been affected by bias.

In the current review, Anna M. Bennet, PhD, of University of Cambridge, England, and colleagues reassessed associations between apoE genotypes and circulating lipid levels and coronary risk. The authors identified 82 studies of lipid levels (86,067 healthy participants) and 121 studies of coronary outcomes (37,850 cases and 82,727 controls), with a focus on studies with at least 1,000 healthy participants for lipids and those with at least 500 coronary outcomes.

The researchers found that in the most extreme comparison, people with the E2/E2 genotype had a 31 percent lower average low-density lipoprotein cholesterol value than those with the E4/E4 genotype, “a difference comparable with that produced by statin medication,” the authors wrote.

“The relationship of apoE genotypes with high-density lipoprotein cholesterol was shallow and inverse and that with triglycerides was nonlinear and largely confined to the E2/E2 genotype, with the latter about 2 times weaker than previously reported.”

“We found that, in comparison with the commonest E3/E3 genotype, E2 carriers had a 20 percent reduced coronary risk, in contrast with previous estimates that E2 carriage is neutral for coronary risk. We noted strong evidence of selective publication in previous estimates based on smaller studies. This is a serious concern given that apoE genotypes and coronary risk had hitherto been considered among the few quantitatively secure associations in cardiovascular disease genetics.”

The researchers add that compared with E3/E3 individuals, E4 carriers had a slightly increased risk of coronary disease.