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Article analyzes relationship of apolipoprotein E genotypes with lipid levels and coronary risk

The JAMA Network Journals

An analysis of previously published studies suggests that there are approximately linear relationships of apolipoprotein E genotypes with lipid levels and with coronary risk, according to a review article in the September 19 issue of JAMA.

Apolipoprotein E (apoE) is a multifunctional protein that plays a key role in the metabolism of cholesterol and triglycerides, according to background information in the article. Some studies have found associations between certain apoE genotypes and lipid levels and coronary risk, but many of those studies were small in size and may be liable to biases.

Anna M. Bennet, Ph.D., of the University of Cambridge, England, and colleagues conducted a review of studies to reassess associations of apoE genotypes with 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 (LDL-C) values than those with the E4/E4 genotype, "a difference comparable with that produced by 'statin' medication," the authors write. "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."

"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 have a slightly increased risk of coronary disease.


(JAMA. 2007;298(11):1300-1311. Available pre-embargo to the media at

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