Age-related macular degeneration (AMD) is the worldwide leading cause of blindness among the elderly, especially in developed countries. The possible association between apolipoprotein E (ApoE) polymorphism (ε2, ε3, ε4) and AMD has been extensively investigated with conflicting results, especially when specifying different clinical phenotypes of AMD. Herein, we conducted a meta-analysis by integrating several recent large-sample studies to verify the effect of ApoE polymorphisms on AMD subtypes.
The retrieve for targeted literature was conducted based on the PubMed, Embase, Cochrane library, and Web of Science. Summary odds ratio (OR) and its 95% confidence intervals (CIs) were used for estimation of risk. The p-value was adjusted due to the multiple comparison.
A total of 12 studies included in the final summary analysis, including 13842 cases and 38647 controls. ApoE ε4 carrier was inversely associated with early stage AMD (OR = 0.889, 95% CI = 0.82-0.97), geographic atrophy (OR = 0.594, 95% CI = 0.43-0.83) and neovascular AMD (OR = 0.670, 95% CI = 0.58-0.76). Stratification analysis by ethnicity revealed that the ApoE ε4 carriers was associated with neovascular AMD in both Caucasians (OR = 0.62, 95% CI = 0.47-0.83) and East Asians (OR = 0.68, 95% CI = 0.58-0.79). A significant association of ApoE ε2 carriers was only found with early AMD in Black and East Asian population, however small samples and limited studies restrict its generalization.
Our meta-analysis revealed a significantly protective role of ε4 on each subtypes of AMD, but no supportive evidence of the association of ε2 with AMD. Thus, further studies with larger samples are needed to understand the precise role of ε2 on AMD susceptibility.