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The 2 and 4 Alleles of the Apolipoprotein Gene Are Associated with Age-Related Macular Degeneration

From the Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia.

PURPOSE. To date, of all the genes studied in relation to age-related macular degeneration (AMD), the alleles of the apolipoprotein (apoE) gene have been the most consistently associated with disease. However, not all apoE studies have found an association, and among these the associations differ. The current study was conducted to investigate further the association of this gene in AMD.

METHODS. Three hundred twenty-two unrelated individuals with diagnosed AMD and 123 unrelated but ethnically matched control subjects were analyzed. All subjects completed a standard questionnaire and were given a fundus examination. A blood sample was collected for DNA extraction. The common allelic variants of apoE were screened through the use of polymerase chain reaction (PCR) and restriction enzyme digestion followed by statistical analysis.

RESULTS. Individuals with the 3 4 genotype of apoE had an approximate halving of disease risk for late (end-stage) AMD (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.34–0.98) relative to the 3 3 genotype at age of ascertainment. Stratification of late AMD into atrophic and neovascular disease revealed that the greatest protective effect for the 3 4 genotype was in individuals with atrophic disease (OR 0.35, 95% CI 0.13–0.92). Men with the 3 4 genotype also showed almost a threefold reduction in risk of disease in late AMD (OR 0.36, 95% CI 0.16–0.82). However, individuals with late AMD and the 2 3 genotype had a significantly earlier mean age of diagnosis of disease (3.4 years, P = 0.015) compared with those with the 3 3 genotype, and this was most evident in women (3.9 years, P = 0.011) and in individuals with neovascular disease (4.7 years, P = 0.003).

CONCLUSIONS. The alleles of apoE appear to have a role in the etiology of AMD, with the 4 allele being protective, or at the very least, delaying the age of diagnosis of disease, whereas the 2 allele appears to have a modifier effect by bringing forward the mean age of disease diagnosis.

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