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 epsilon 2/epsilon 3/epsilon 4 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 epsilon 2/epsilon 3/epsilon 4 polymorphism of Apo E gene. Overall comparison of alleles epsilon 2 with epsilon 3 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 epsilon 4 with epsilon 3 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 epsilon 4 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 epsilon 4 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 epsilon 4 allele is a risk factor of gallbladder stone disease, especially in elder people and Chinese population.