Arms2 A69s Polymorphism And The Risk For Age-related Maculopathy: The Alienor Study

Abstract

 

Purpose:

 

Data from population-based epidemiological studies are necessary in order to better estimate the associations of ARMS2 (LOC387715) with age-related maculopathy (ARM). In particular, few data are available on early ARM.

 

Methods:

 

The Alienor Study is a population-based study on nutrition and age-related eye diseases. 963 subjects had an eye examination from September 2006 to May 2008 in Bordeaux (France). ARM was classified from colour photographs in five exclusive stages: late neovascular ARM; late atrophic ARM (geographic atrophy); early ARM2 (large soft indistinct drusen and/or reticular drusen and/or large distinct drusen with pigment abnormalities); early ARM1 (large soft distinct drusen alone or pigment abnormalities alone); no ARM. ARMS2 A69S polymorphism (rs10490924) was determined from blood collected in 1999-2001. Associations were estimated using logistic Generalized Estimating Equations (GEE) models, subjects without ARM being the reference. Analyses were adjusted for age, gender, Complement Factor H (CFH) Y402H polymorphism and smoking.

 

Results:

 

Of 963 subjects, 738 subjects had complete data, representing 1424 gradable eyes. By comparison with GG subjects, TT subjects were at increasing risk for early ARM1 (OR=4.60, 95 % confidence interval (CI): 1.54-13.7, p=0.006), early ARM2 (OR=13.8, 95 % CI: 5.17-36.7, p<0.0001), late atrophic ARM (OR=23.6, 95 % CI: 5.28-105.7, p<0.0001) and late neovascular ARM (OR=16.1, 95 % CI: 3.32-78.6, p=0.0006). By contrast, associations of the different types of ARM with the GT genotype were modest (OR ranging from 1.52 to 2.47) and reached statistical significance only for early ARM1 (OR=1.52, 95 % CI: 1.03-2.23, p=0.04). Smoking and CFH Y402H remained independently associated with ARM, after controlling for ARMS A69S genotypes.

 

Conclusions:

 

This population-based study confirms the major contribution of the TT genotype of ARMS2 A69S polymorphism in early and late ARM. This association is independent from the other two major risk factors (smoking and CFH Y402H polymorphism).

 

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