Original Contribution Apolipoprotein E Gene Associations in Age-related Macular Degeneration

The apolipoprotein E gene (APOE) has been found to be associated with age-related macular degeneration (AMD). Reported associations have been questioned, as they are opposite those for Alzheimer’s disease and cardiovascular disease. The authors examined associations between APOE genotype and AMD using a casecontrol study (2,287 cases and 2,287 controls individually matched on age, sex, and country of origin) nested within Melbourne Collaborative Cohort Study participants aged 48–86 years at AMD detection. The odds ratio for early AMD among participants with e2-containing genotypes (e2e2/e2e3/e2e4) was 1.32 (95% confidence interval (CI): 1.11, 1.58; P 1⁄4 0.002) versus persons with genotype e3e3. Associations with early AMD varied by smoking status; e2-containing genotypes were positively associated with early AMD for never and previous smokers (never smokers: odds ratio (OR)1⁄4 1.40, 95%CI: 1.12, 1.76 (P1⁄4 0.003); previous smokers: OR1⁄4 1.39, 95%CI: 1.00, 1.93 (P 1⁄4 0.05)) but not for current smokers (OR 1⁄4 0.66, 95% CI: 0.34, 1.30 (P 1⁄4 0.2; interaction P 1⁄4 0.05). The e4containing genotype group (e3e4/e4e4) had an inverse association with early AMD among current smokers only (OR 1⁄4 0.41, 95% CI: 0.22, 0.77 (P 1⁄4 0.005)). These results highlight the importance of stratifying by smoking status in elderly populations. Smokers who survive to old age may be more likely to possess unknown genotypes which modify exposure-disease associations.