Apolipoprotein E Gene Associations in Age-Related Macular Degeneration: The Melbourne Collaborative Cohort Study

Am J Epidemiol. 2012 Mar 15;175(6):511-8. doi: 10.1093/aje/kwr329. Epub 2012 Feb 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Effect Modifier, Epidemiologic
  • Genetic Predisposition to Disease
  • Genotype
  • Genotyping Techniques
  • Humans
  • Logistic Models
  • Macular Degeneration / etiology
  • Macular Degeneration / genetics*
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Smoking / adverse effects

Substances

  • Apolipoproteins E