There are linear links between apolipoprotein E (apoE) genotypes with lipid levels and coronary risk, according to an analysis of previous studies published in the Journal of the American Medical Association (JAMA).
apoE, a multifunctional protein, plays a vital part in cholesterol and triglycerides metabolism, explain the writers. A number of studies have identified a link between some apoE genotypes and lipid levels and coronary risk. However, the majority of those studies were small and perhaps biased.
Anna M. Bennet, Ph.D., University of Cambridge, England, and team looked at a number of studies in order to see whether there was really a link between apoE with circulating lipid levels and coronary risk. There were 82 studies of lipid levels, involving 86,067 healthy subjects, and 121 studies of coronary outcomes – 37,850 cases and 82,727 controls – with a focus on studies with 1,000 healthy subjects or more for lipids and those with 500 or more coronary outcomes.
In the most extreme comparison, the scientists explained, individuals with the E2/E2 genotype had 31% lower average LDL-C (low-density lipoprotein cholesterol) values compared to people with the E4/E4 genotype. The authors wrote “…a difference comparable with that produced by ‘statin’ medication. The relationship of apoE genotypes with high-density lipoprotein cholesterol (HDL-C) 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.”
The researchers added “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.”
E4 carriers have a slightly higher risk of coronary disease compared with E3/E3 individuals, the authors wrote.
JAMA. 2007;298(11):1300-1311
Written by: Christian Nordqvist