Association of the apolipoprotein E gene with age-related macular degeneration: possible effect modification by family history, age, and gender

Mol Vis. 2000 Dec 31:6:287-93.


Purpose: Age-related macular degeneration (AMD) is a complex disorder affecting older adults in which genetic factors are likely to play a role. It has been previously suggested that the e4 allele of the apolipoprotein E (APOE) gene may have a protective effect on AMD risk and that the e2 allele may increase disease risk. The purpose of our study was to examine whether an independent data set would support the proposed role of APOE in AMD etiology.

Methods: We compared AMD cases (n=230) to controls (n=372) with respect to APOE genotypes using c2 tests and logistic regression analysis. We also conducted separate analyses for familial (n=129) and sporadic (n=101) AMD cases since these groups may have a different disease etiology.

Results: We did not find evidence for the risk-increasing effect attributed to the e2 allele in either familial or sporadic AMD. No evidence for a protective effect of the e4 allele was obtained for sporadic AMD. The age- and sex-adjusted odds ratio (OR) for e4 carriers among familial AMD cases compared to controls was 0.66 (95% confidence interval: 0.38-1.12, p=0.13). In the subgroup of individuals younger than 70 years of age, an OR of 0.24 (95% confidence interval: 0.08-0.72, p=0.004) was obtained.

Conclusions: Our data modestly support a protective effect of the APOE-e4 allele on AMD risk, but emphasize the need to investigate more thoroughly whether the effect could be restricted to cases with a family history of AMD and whether it varies across age and sex groups.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Alleles
  • Apolipoproteins E / genetics*
  • DNA / analysis
  • Family Health
  • Female
  • Genotype
  • Humans
  • Macular Degeneration / genetics*
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk Factors
  • Sex Factors


  • Apolipoproteins E
  • DNA