Estrogen Receptor Alpha Gene Polymorphisms Are Associated With Incident Late Ageing Macular Disease: The Rotterdam Study

Abstract

Purpose: : It has been suggested that early menopause increases the risk of aging macular disease (AMD) and that postmenopausal exogenous estrogens reduce this risk. Estrogen mediates its effect through binding to estrogen receptors (ERs) that, once activated, regulate the expression of multiple genes. We investigated whether a known genetic variation at the ER gene is a risk factor for AMD.

Methods: : In a prospective population–based cohort study of participants aged 55 years and older, associations between ERα PvuII–XbaI haplotypes and incident early or late AMD were studied in 4914 participants after a mean follow–up time of 7.7 years. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: : ERα PvuII–XbaI haplotype 1 was a risk factor for late AMD in an allele–dose manner. Homozygous carriers were at 3.20 (95% CI: 1.47–6.99) times higher risk for late AMD than non–carriers of haplotype 1, and this was most pronounced for wet AMD (HR 4.71; 95% CI 1.62–13.66). Correction for additional covariates did not essentially alter our findings.

Conclusions: : Carriers of ERα PvuII–XbaI haplotype 1 have an increased risk of late AMD and especially of the wet form, with similar estimates in men and women.

Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: risk factor assessment • candidate gene analysis