Meta-analysis for the Association of Apolipoprotein E ε2/ε3/ε4 Polymorphism with Coronary Heart Disease.
Level 3 - non-randomized controlled study
Meta-analysis of observational case-control studies.
PubMed 25963363 · doi:10.4103/0366-6999.156803
What was done
The authors conducted a meta-analysis of 14 published case-control studies comprising 5,746 coronary heart disease (CHD) cases and 19,120 controls to assess the relationship between apolipoprotein E (APOE) ε2/ε3/ε4 polymorphisms and CHD risk. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models, and publication bias was assessed and adjusted with the trim-and-fill method.
What was found
Carriers of the APOE ε2 allele had a significantly reduced risk of CHD compared with the ε3 allele (ε2 vs. ε3 allele: OR = 0.82, 95% CI: 0.75–0.90, P < 0.001; ε2 carriers vs. ε3 carriers: OR = 0.81, 95% CI: 0.73–0.89, P < 0.001), especially in Caucasian populations. Conversely, the ε4 allele was associated with a significantly increased risk of CHD (ε4 vs. ε3 allele: OR = 1.34, 95% CI: 1.15–1.57, P < 0.001), especially in Mongoloid populations. Potential publication bias was observed for the ε4 versus ε3 genetic model, but results remained consistent after trim-and-fill adjustment.
Why it matters
This study clarifies discordant literature by synthesizing evidence showing opposite directional effects of APOE variants on CHD, indicating a protective effect for ε2 and increased susceptibility for ε4.
Limits
The included primary studies were retrospective case-control designs, and risk estimates were crude odds ratios unadjusted for potential confounders such as lipid levels, smoking, age, or comorbidities. Potential publication bias was present for the ε4 analysis, and findings showed ancestral heterogeneity.
Cited by
- 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.