Purchase this article with an account.
Digna R. Velez Edwards, Paul Gallins, Monica Polk, Juan Ayala-Haedo, Stephen G. Schwartz, Jaclyn L. Kovach, Kylee Spencer, Gaofeng Wang, Anita Agarwal, Eric A. Postel, Jonathan L. Haines, Margaret Pericak-Vance, William K. Scott; Inverse Association of Female Hormone Replacement Therapy with Age-Related Macular Degeneration and Interactions with ARMS2 Polymorphisms. Invest. Ophthalmol. Vis. Sci. 2010;51(4):1873-1879. doi: 10.1167/iovs.09-4000.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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).
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).
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.
This PDF is available to Subscribers Only