Inverse association of female hormone replacement therapy with age-related macular degeneration and interactions with ARMS2 polymorphisms.

Journal Article (Journal Article)

Purpose. To investigate whether female reproductive history and hormone replacement therapy (HRT) or birth control pills (BCPs) influence risk for age-related macular degeneration (AMD) and whether genetic factors interact with HRT to modulate AMD risk. Methods. Related and unrelated female participants (n = 799) were examined and data were analyzed with generalized estimating equations with adjustment for age and smoking. Individuals with AMD grades 1 to 2 were considered to be unaffected (n = 239) and those with grades 3 to 5 were considered affected (n = 560). Results. When comparing all cases with controls, significant inverse associations were observed for HRT (odds ratio [OR] = 0.65, 95% CI 0.48-0.90, P = 0.008) and BCPs (OR = 0.60, 95% CI 0.36-0.10, P = 0.048). When analyses were stratified by AMD severity (early versus geographic atrophy versus neovascular), the inverse association remained significant (HRT OR = 0.45, 95% CI 0.30-0.66, P < 0.0001; BCP OR = 0.55, 95% CI 0.32-0.96, P = 0.036) only when comparing neovascular AMD with the control. All pair-wise HRT-genotype and BCP-genotype interactions were examined, to determine whether HRT or BCP modifies the effect of established genetic risk factors. The strongest interactions were observed for HRT x ARMS2 coding SNP (R73H) rs10490923 (P = 0.007) and HRT x ARMS2 intronic SNP rs17623531 (P = 0.019). Conclusions. These findings provide the first evidence suggesting that ARMS2 interacts with HRT to modulate AMD risk and are consistent with previous reports demonstrating a protective relationship between exogenous estrogen use and neovascular AMD. These results highlight the genetic and environmental complexity of the etiologic architecture of AMD; however, further replication is necessary to validate them.

Full Text

Duke Authors

Cited Authors

  • Edwards, DRV; Gallins, P; Polk, M; Ayala-Haedo, J; Schwartz, SG; Kovach, JL; Spencer, K; Wang, G; Agarwal, A; Postel, EA; Haines, JL; Pericak-Vance, M; Scott, WK

Published Date

  • April 2010

Published In

Volume / Issue

  • 51 / 4

Start / End Page

  • 1873 - 1879

PubMed ID

  • 19933179

Pubmed Central ID

  • PMC2868389

Electronic International Standard Serial Number (EISSN)

  • 1552-5783

Digital Object Identifier (DOI)

  • 10.1167/iovs.09-4000


  • eng

Conference Location

  • United States