A Meta-Analysis of Apolipoprotein E Gene ε2/ε3/ε4 Polymorphism for Gallbladder Stone Disease

BACKGROUND: Numerous studies have investigated the relationship between apolipoprotein (Apo) E gene polymorphisms and gallbladder stone disease (GSD) across ethnic populations; however, the results are often inconsistent. This meta-analysis aims to comprehensively evaluate the influence of a common ε2/ε3/ε4 polymorphism in Apo E gene on the risk of gallbladder stone disease. METHOD: Data were analyzed using the RevMan software (V5.1) and a random-effects model was applied irrespective of between-study heterogeneity. Publication bias was weighed using the fail-safe number. RESULTS: There were 17 study populations totaling 1773 cases and 2751 controls for ε2/ε3/ε4 polymorphism of Apo E gene. Overall comparison of alleles ε2 with ε3 in all study populations yielded a 16% decreased risk for GSD (95% confidence interval [95% CI]: 0.68–1.05; P = 0.31; I(2) = 13%), and comparison of alleles ε4 with ε3 yielded a 25% increased risk (95% confidence interval [95% CI]: 0.97–1.61; P = 0.0003; I(2) = 63%). Subgroup analysis by study design indicated that the magnitude of association in hospital-based studies was largely significantly strengthened for ε4 allelic model (odds ratio [OR] = 1.46; 95% CI: 1.05–2.02; p = 0.0007; I(2) = 65%). Subgroup analysis by age of controls indicated a remarkably significant elevation in the magnitude of association in age >50 subgroups in ε4 allelic model (OR = 1.50; 95% CI: 1.03–2.19; p = 0.0009; I(2) = 72%). Moreover, subgroup analysis by cases gender indicated a reduction in the magnitude of association in male<30% studies for E2/2 genotypic model (OR = 0.32; 95% CI: 0.07–1.49; p = 0.16; I(2) = 45%). CONCLUSIONS: Our results reveal that Apo E gene ε4 allele is a risk factor of gallbladder stone disease, especially in elder people and Chinese population.