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American Journal of Epidemiology Advance Access originally published online on August 17, 2006
American Journal of Epidemiology 2006 164(9):813-822; doi:10.1093/aje/kwj279
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Human Genome Epidemiology (HuGE) Review

Association between Apolipoprotein E Polymorphisms and Age-related Macular Degeneration: A HuGE Review and Meta-Analysis

Ammarin Thakkinstian1,2, Steve Bowe2, Mark McEvoy2, Wayne Smith2 and John Attia2

1 Clinical Epidemiology Unit, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
2 Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, New South Wales, Australia

Correspondence to Dr. John Attia, Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, New South Wales, 2300 Australia (e-mail: John.Attia{at}newcastle.edu.au).

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 E2 and E4 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 E2 and a protective effect of up to 40% for E4. E2 appeared to act in a recessive mode and E4 in a dominant mode. There appears to be a differential effect of the E2 and E4 alleles on the risk of age-related macular degeneration, although the possibility of survivor bias needs to be ruled out more definitively.

ApoE; apolipoproteins E; epidemiology; genetics; macular degeneration; meta-analysis; polymorphism, genetic

Abbreviations: AMD, age-related macular degeneration; ApoE, apolipoprotein E; CI, confidence interval; OR, odds ratio

Editor's note: This article is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/default.htm).


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