Meta-analysis for the Association of Apolipoprotein E ε2/ε3/ε4 Polymorphism with Coronary Heart Disease

Background: Coronary heart disease (CHD) is a multifactorial disease and is thought to have a polygenic basis. Apolipoprotein E (APOE) gene is one such candidate with its common epsilon 2/epsilon 3/epsilon 4 polymorphism in CHD. In recent years, numerous case-control studies have investigated the relationship of APOE polymorphism with CHD risk. However, the results are confusing. Methods: To clarify this point, we undertook a meta-analysis based on 14 published studies including 5746 CBD cases and 19,120 controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for association using a random-effects or fixed-effects model using STATA version 10 (StataCorp LP, College Station, TX, USA). Results: Overall, the analysis showed that carriers of APOE epsilon 2 allele decreased risk for CHD (epsilon 2 allele vs. epsilon 3 allele: OR = 0.82, 95% CI: 0.75-0.90, P < 0.001; epsilon 2 carriers vs. epsilon 3 carriers: OR = 0.81, 95% CI: 0.73-0.89, P < 0.001), compared with those carrying epsilon 3 allele, especially in Caucasian population. However, those with epsilon 4 allele had a significant increased risk for CHD (epsilon 4 allele vs. epsilon 3 allele: OR = 1.34, 95% CI: 1.15-1.57, P < 0.001), especially in Mongoloid population. Potential publication bias was observed in the genetic model of ELI versus epsilon 3, but the results might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results were not materially alerted, suggesting the stability of our results. Conclusions: Taken together, our meta-analysis supported a genetic association between APOE gene and CHD. epsilon 4 increased the risk of CHD, whereas epsilon 2 decreased the risk of CBD.