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K. Spencer, K. Glenn, K. Brown-Gentry, D. Murdock, J. A. Canter, J. L. Haines, M. D. Ritchie, D. C. Crawford; Epidemiologic Architecture for Genes Linked to Environment (EAGLE): Association of ARMS2 A69S With Age-Related Macular Degeneration in the National Health and Nutrition Examination Surveys. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1258.
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The ARMS2 A69S rs10490924 polymorphism is strongly associated with age-related macular degeneration (AMD) in Caucasians, but little is known about its effect in other U.S. populations. We, as part of the Population Architecture using Genomics and Epidemiology (PAGE) Study, are genotyping samples from the National Health and Nutrition Examination Surveys (NHANES), a cross-sectional survey of Americans representing at least three major groups: non-Hispanic whites (n=6605), non-Hispanic blacks (n=3442), and Mexican-Americans (n=3949). We examined the frequency of ARMS2 A69S in these diverse groups, and tested for association with AMD in the subset of participants with fundus photographs available. We also tested for an association between genotype and serum lutein/zeaxanthin levels, the major component of macular pigment.
AMD cases were defined as participants 60 years of age and older with a summary AMD score of 1 or 2, corresponding to early and late AMD, respectively (n=190 W, 30 B, 47 MA). Controls were at least 60 years of age with a summary AMD score of 0 (n=664 W, 209 B, 270 MA). Associations with AMD and serum lutein/zeaxanthin were tested using logistic and linear regression, respectively, in both unadjusted and adjusted models assuming an additive genetic model. Adjusted models included age, gender, and body mass index (BMI).
The minor allele frequency of ARMS2 A69S was similar across groups (W=0.22, B=0.24, MA=0.25). A69S was associated with AMD in all groups in adjusted and unadjusted models (p-value, odds ratio (OR) and 95% confidence interval for adjusted models, W: p<0.0001, OR=1.9(1.4-2.5), B: p=0.04, OR=0.44(0.19-0.97), MA: p=0.04, OR=1.7(1.0-2.7). A69S trended towards significance with serum lutein/zeaxanthin levels in whites (p=0.07 in adjusted and unadjusted models), but not in blacks or MA (p>0.60 in all models).
The association of ARMS2 A69S with AMD is common to all three groups. Interestingly, the direction of the effect was reversed in blacks compared to whites and MA.While this could reflect a true gene*ethnicity interaction, it is more likely a result of sampling variation, given the small sample sizes. The association with lutein/zeaxanthin levels in whites suggests that perhaps the link between ARMS2 and AMD is through carotenoid metabolism.
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