Apolipoprotein e gene associations in age-related macular degeneration
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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 case-control 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 = 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) = 1.40, 95 CI: 1.12, 1.76 (P = 0.003); previous smokers: OR = 1.39, 95 CI: 1.00, 1.93 (P = 0.05)) but not for current smokers (OR = 0.66, 95 CI: 0.34, 1.30 (P = 0.2; interaction P = 0.05). The e4-containing genotype group (e3e4/e4e4) had an inverse association with early AMD among current smokers only (OR = 0.41, 95 CI: 0.22, 0.77 (P = 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.