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In this study, the authors sought to determine whether single nucleotide polymorphisms in the estrogen receptor alpha (ESR1) and matrix metalloproteinase 2 (MMP2) genes are associated with age-related maculopathy (ARM) in older women. Subjects comprised a random sample of Caucasian women aged > or =74 years participating in the Study of Osteoporotic Fractures year 10 follow-up (n = 906) in 1997-1998. Fundus photographs were graded for ARM using a modification of the Wisconsin Age-Related Maculopathy Grading System. The prevalences of early ARM and late ARM were 46% and 4%, respectively. The MMP2 rs2287074 single nucleotide polymorphism (G-->A) was associated with ARM. The A allele was present in 47%, 43%, and 30% of subjects with no, early, and late ARM, respectively (p = 0.01), and was associated with lower odds of any ARM (for AG vs. GG, odds ratio = 0.80, 95% confidence interval: 0.65, 0.99; for AA vs. GG, odds ratio = 0.64, 95% confidence interval: 0.42, 0.98). An interaction with use of postmenopausal hormone therapy was significant (p = 0.02). The MMP2 rs2287074 A allele may be associated with a lower likelihood of ARM in older Caucasian women, particularly those who have never used hormone therapy. The role of MMP2 rs2287074 in ARM should be further elucidated. [ABSTRACT FROM AUTHOR]