Association between apolipoprotein E polymorphisms and age-related macular degeneration: A HuGE review and meta-analysis

A possible association between apolipoprotein E polymorphisms and age-related macular degeneration has been investigated numerous times, with conflicting results. A previous analysis pooling results from four studies (Schmidt et al., Ophthalmic Genet 2002;23:209-23) suggested an association, but those investigators did not document allele frequencies, the magnitude of the association, or the possible genetic mode of action. Thus, the authors searched MEDLINE from 1966 to December 2005 for any English-language studies reporting genetic associations. Data and study quality were assessed in duplicate. Pooling was performed while checking for heterogeneity and publication bias. Frequencies of the E-2 and E-4 alleles in Caucasians were approximately 8% and 15%, respectively. Allele- and genotype-based tests of association indicated a risk effect of up to 20% for E-2 and a protective effect of up to 40% for E-4. E-2 appeared to act in a recessive mode and E-4 in a dominant mode. There appears to be a differential effect of the E-2 and E-4 alleles on the risk of age-related macular degeneration, although the possibility of survivor bias needs to be ruled out more definitively.