Apolipoprotein E gene associations in age-related macular degeneration: the Melbourne Collaborative Cohort Study.
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.
Center for Eye Research Australia, University of Melbourne/Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia. madam@student.unimelb.edu.au
Madeleine K M
MK
Adams
Julie A
JA
Simpson
Andrea J
AJ
Richardson
Dallas R
DR
English
Khin Zaw
KZ
Aung
Galina A
GA
Makeyeva
Robyn H
RH
Guymer
Graham G
GG
Giles
John
J
Hopper
Liubov D
LD
Robman
Paul N
PN
Baird
D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D015987:Effect Modifier, Epidemiologic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D016015:Logistic Models; D008268:Macular Degeneration / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012907:Smoking / Q000009:adverse effects
D001057:Apolipoproteins E