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The Rotterdam Study

Simone de Voogd, MD, PhD; Roger C. W. Wolfs, MD, PhD; Nomdo M. Jansonius, MD, PhD; André G. Uitterlinden, PhD; Huibert A. P. Pols, MD, PhD; Albert Hofman, MD, PhD; Paulus T. V. M. de Jong, MD, PhD, FEBOphth, FRCOphth

Arch Ophthalmol. 2008;126(1):110-114.

Objective  To investigate whether polymorphisms in the estrogen receptor alpha (ESR1) and beta (ESR2) genes were a risk factor for open-angle glaucoma (OAG).

Methods  Participants 55 years and older from the population-based Rotterdam Study underwent, at baseline and at follow-up, the same ophthalmic examination, including visual field screening and stereo optic disc photography. A diagnosis of OAG was based on an algorithm using optic disc measures and visual field loss. Haplotypes of the ESR1 and ESR2 genes were determined.

Results  We diagnosed incident OAG in 87 of 3842 participants (2.3%) at risk after a mean follow-up of 6.5 years. We could not detect any association with ESR1 haplotypes. Haplotype 1 of ESR2 showed a 3.6-fold (95% confidence interval, 1.4-9.2) higher risk of incident OAG in men. In women, no association was found between ESR2 and incident OAG.

Conclusion  Polymorphisms in the ESR1 gene are unrelated to OAG, but ESR2 polymorphisms seem to lead to increased risk of OAG in men.

Author Affiliations: Departments of Epidemiology & Biostatistics (Drs de Voogd, Wolfs, Jansonius, Uitterlinden, Pols, Hofman, and de Jong), Ophthalmology (Dr Wolfs), and Internal Medicine (Drs Uitterlinden and Pols), Erasmus Medical Center, Rotterdam; Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen (Dr Jansonius); the Netherlands Institute for Neurosciences, Royal Netherlands Academy of Arts and Sciences (Dr de Jong), and Department of Ophthalmology, Academic Medical Center, Amsterdam (Dr de Jong), the Netherlands.

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