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PLoS One. 2012;7(9):e45849. doi: 10.1371/journal.pone.0045849. Epub 2012 Sep 25.

A meta-analysis of apolipoprotein E gene ε2/ε3/ε4 polymorphism for gallbladder stone disease.

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Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.



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.


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.


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%).


Our results reveal that Apo E gene ε4 allele is a risk factor of gallbladder stone disease, especially in elder people and Chinese population.

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