Association of apolipoprotein E genotypes with lipid levels and coronary risk.
Level 3 - non-randomized controlled study
Meta-analysis of observational and genetic association studies
PubMed 17878422 · doi:10.1001/jama.298.11.1300
What was done
Authors conducted a systematic review and meta-analysis of published and unpublished studies (January 1970–January 2007) identified via MEDLINE, EMBASE, BIOSIS, Science Citation Index, CNKI, reference lists, and registries. The analysis evaluated associations of apolipoprotein E (apoE) genotypes with circulating lipid levels (82 studies, 86,067 healthy participants) and coronary outcomes (121 studies, 37,850 cases and 82,727 controls), focusing primarily on studies with at least 1,000 healthy participants for lipids and at least 500 cases for coronary outcomes.
What was found
Linear relationships were observed for apoE genotypes (ordered epsilon2/epsilon2, epsilon2/epsilon3, epsilon2/epsilon4, epsilon3/epsilon3, epsilon3/epsilon4, epsilon4/epsilon4) with LDL-C and coronary risk. Comparing extremes, epsilon2/epsilon2 individuals had 1.14 mmol/L (95% CI, 0.87–1.40 mmol/L [44.0 mg/dL; 95% CI, 33.6–51.1 mg/dL]) or about 31% (95% CI, 23%–38%) lower mean LDL-C than epsilon4/epsilon4 individuals. Relative to epsilon3/epsilon3, the odds ratio for coronary disease was 0.80 (95% CI, 0.70–0.90) in epsilon2 carriers and 1.06 (95% CI, 0.99–1.13) in epsilon4 carriers. The association with HDL-C was inverse and shallow, while triglyceride associations were non-linear and largely confined to epsilon2/epsilon2.
Why it matters
This large meta-analysis clarifies the relationship between lifelong genetically determined apoE variation, circulating lipid subfractions, and coronary disease risk.
Limits
The underlying studies were observational and liable to population stratification and unmeasured confounding. The coronary risk increase for epsilon4 carriers had a 95% confidence interval that spanned the null (0.99 to 1.13). Abstract lacks data on specific coronary endpoints, statin use, or ethnic subgroups.
Cited by
- supports Once corrected for LDL particle number or ApoB, the increased risk of cardiovascular disease from APOE 4/4 or 3/4 genotypes disappears.
- supports The APOE2 allele is protective against cardiovascular disease, and an APOE 2/4 genotype has approximately the same cardiac risk as APOE 3/3.