American Journal of Epidemiology Advance Access originally published online on March 20, 2008
American Journal of Epidemiology 2008 167(10):1217-1225; doi:10.1093/aje/kwn024
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ORIGINAL CONTRIBUTIONS |
Estrogen Receptor Alpha and Matrix Metalloproteinase 2 Polymorphisms and Age-related Maculopathy in Older Women
1 Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
2 Biogen Idec, Inc., San Diego, CA
3 Omics Laboratory, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA
4 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
5 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
6 Center for Chronic Disease Outcomes Research, Veterans Affairs Medical Center, Minneapolis, MN
7 Departments of Medicine, Epidemiology, and Community Health, Schools of Medicine and Public Health, University of Minnesota, Minneapolis, MN
8 Research Institute, California Pacific Medical Center, San Francisco, CA
9 Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, CA
10 Division of Rheumatology, School of Medicine, University of Maryland, Baltimore, MD
11 Kaiser Permanente Center for Health Research, Northwest/Hawaii, Portland, OR
12 Departments of Human Genetics and Biomathematics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
13 Department of Biostatistics, School of Public Health, University of California, Los Angeles, Los Angeles, CA
14 Department of Epidemiology, School of Public Health, University of California, Los Angeles, Los Angeles, CA
Correspondence to Dr. Robin L. Seitzman, Drug Safety and Risk Management, Biogen Idec, Inc., 5200 Research Place, San Diego, CA 92122 (e-mail: seitzman{at}ucla.edu).
Received for publication September 14, 2007. Accepted for publication January 23, 2008.
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 
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.
estrogen receptor alpha; macular degeneration; matrix metalloproteinase 2; polymorphism, single nucleotide
Abbreviations: ARM, age-related maculopathy; ESR1, estrogen receptor alpha; MMP2, matrix metalloproteinase 2; PCR, polymerase chain reaction; RPE, retinal pigment epithelium; SNP, single nucleotide polymorphism; SOF, Study of Osteoporotic Fractures