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Apolipoprotein E gene associations in age-related macular degeneration: the Melbourne Collaborative Cohort Study
Madeleine K M Adams1, Julie A Simpson, Andrea J Richardson
1Center for Eye Research Australia, University of Melbourne/Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia. madam@student.unimelb.edu.au
Abstract:
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 ε2-containing genotypes (ε2ε2/ε2ε3/ε2ε4) was 1.32 (95% confidence interval (CI): 1.11, 1.58; P = 0.002) versus persons with genotype ε3ε3. Associations with early AMD varied by smoking status; ε2-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 ε4-containing genotype group (ε3ε4/ε4ε4) 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.
Insights
The apolipoprotein E gene (APOE) ε2 genotype increases early age-related macular degeneration (AMD) risk, particularly in non-smokers. Smoking modifies the association between APOE genotypes and AMD in older adults.
Area of Science:
- Ophthalmology
- Genetics
- Epidemiology
Background:
- Apolipoprotein E (APOE) gene variants are implicated in age-related macular degeneration (AMD), but associations require clarification due to conflicting data.
- Previous studies suggest APOE genotype associations with AMD are opposite to those observed for Alzheimer's disease and cardiovascular disease.
Purpose of the Study:
- To investigate the association between APOE genotype and age-related macular degeneration (AMD).
- To explore how smoking status modifies the relationship between APOE genotype and AMD risk in an elderly population.
Main Methods:
- A case-control study nested within the Melbourne Collaborative Cohort Study.
- Involved 2,287 cases and 2,287 individually matched controls aged 48-86 years at AMD detection.
- Analysis stratified by smoking status to assess gene-environment interactions.
Main Results:
- APOE ε2-containing genotypes showed a positive association with early AMD (OR=1.32, P=0.002) compared to ε3ε3.
- This association was significant for never smokers (OR=1.40) and previous smokers (OR=1.39), but not current smokers (OR=0.66).
- APOE ε4-containing genotypes were inversely associated with early AMD only in current smokers (OR=0.41, P=0.005).
Conclusions:
- Smoking status is a critical factor that modifies the association between APOE genotype and early AMD.
- Findings emphasize the need to stratify analyses by smoking status in elderly populations to understand AMD etiology.
- Unidentified genetic factors in long-term smokers may influence exposure-disease associations.
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