Lack of Association of Apolipoprotein E (Apo E) ε2/ε3/ε4 Polymorphisms with Primary Open-Angle Glaucoma: A Meta-Analysis from 1916 Cases and 1756 Controls

Background: A number of case-control studies were conducted to investigate the association of apolipoprotein E (Apo E) polymorphisms with primary open angle glaucoma (POAG). But the results remain controversial. This meta-analysis aims to comprehensively evaluate the relationship between a common ε2/ε3/ε4 polymorphism in Apo E gene on the risk of POAG. Method: A comprehensive literature search for studies published up to April 2013 was performed. Summary odds ratios (ORs) and 95% confidence intervals (CI) were calculated employing random-effects models irrespective of between-study heterogeneity. Publication bias of literatures was evaluated using funnel plots and Egger's test. Results: A total of 12 studies including 1916 cases and 1756 controls meeting the predefined criteria were involved in this meta-analysis. Overall, the Apo E ε2 allele and ε4 allele were not associated with POAG, compared with those carrying ε3 allele, with ORs of 0.98 (95% CI, 0.79 to 1.23; P = 0.872) and 1.05 (95% CI, 0.78 to 1.41; P = 0.743), respectively. Genotypic analysis also found no significant association between the ε4 carriers (ε3/ε4+ε4/ε4), ε2 carriers (ε2/ε3+ε2/ε2) and POAG, compared with participants with Apo E ε3/3, with ORs of 0.91 (95% CI, 0.66 to 1.25; P = 0.543) and 1.08 (95% CI, 0.74 to 1.57; P = 0.694), respectively. In the subgroup analysis by ethnicity, source of controls, genotyping methods, Hardy-Weinberg equilibrium or not, or type of the POAG, still no obvious associations were found. Conclusions: This meta-analysis suggests that Apo E ε2/ε3/ε4 polymorphisms may not be associated with the risk of POAG. However, well-designed studies with larger sample size and more ethnic groups are required to further validate the results.