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(Investigative Ophthalmology and Visual Science. 2004;45:1306-1310.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.03-1253
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Association of Apolipoprotein E Alleles with Susceptibility to Age-Related Macular Degeneration in a Large Cohort from a Single Center

Sepideh Zareparsi,1 Adam C. Reddick,1 Kari E. H. Branham,1 Kathryn B. Moore,1 Laurie Jessup,1 Susan Thoms,1 Michael Smith-Wheelock,1 Beverly M. Yashar,1,2 and Anand Swaroop1,2

1From the Departments of Ophthalmology and Visual Sciences and 2Human Genetics, University of Michigan, Ann Arbor, Michigan.

PURPOSE. To examine the effect of apolipoprotein E (APOE) alleles on age-related macular degeneration (AMD) risk and on age at diagnosis of AMD in a large patient cohort recruited from a single center.

METHODS. The frequency of APOE alleles was analyzed in 632 unrelated AMD patients and 206 unrelated controls, all of whom were of white ancestry. The presence or absence of disease symptoms in all patients and controls was based on clinical examination and/or ophthalmic records. The association with APOE was explored in the context of AMD subtypes, family history status, possible interaction with smoking, and distribution of age at diagnosis of AMD.

RESULTS. The frequency of the {epsilon}4 allele was significantly reduced in patients compared with controls (0.10 vs. 0.14, P <= 0.02). Gender- and age-adjusted odds ratios indicated that {epsilon}4-carriers have significantly lower risk of developing AMD compared to {epsilon}3{epsilon}3 subjects (OR = 0.55, 95% CI: 0.37–0.82, P = 0.004). In the cohort, AMD patients with a positive family history exhibited a significant 3.5 years earlier age at diagnosis (P = 0.001); however, APOE alleles did not appear to modulate the age at diagnosis of AMD.

CONCLUSIONS. The association between the APOE-{epsilon}4 allele and a reduced risk of AMD was established in a large cohort with sufficient statistical power. How distinct APOE alleles affect AMD susceptibility warrants further investigation.




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