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Table. Associations of the Different Types of Age-Related Maculopathy With ARMS2 A69S Genotypes, Adjusted for Age, Sex, CFH Y402H Genotypes, and Smoking
Table. Associations of the Different Types of Age-Related Maculopathy With ARMS2 A69S Genotypes, Adjusted for Age, Sex, CFH Y402H Genotypes, and Smoking
1.
Rivera A, Fisher SA, Fritsche LG,  et al.  Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk.  Hum Mol Genet. 2005;14(21):3227-3236PubMedArticle
2.
Jakobsdottir J, Conley YP, Weeks DE, Mah TS, Ferrell RE, Gorin MB. Susceptibility genes for age-related maculopathy on chromosome 10q26.  Am J Hum Genet. 2005;77(3):389-407PubMedArticle
3.
Delcourt C, Korobelnik JF, Barberger-Gateau P,  et al.  Nutrition and age-related eye diseases: the ALIENOR (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) Study.  J Nutr Health Aging. 2010;14(10):854-861PubMedArticle
4.
Bird AC, Bressler NM, Bressler SB,  et al; International ARM Epidemiological Study Group.  An international classification and grading system for age-related maculopathy and age-related macular degeneration.  Surv Ophthalmol. 1995;39(5):367-374PubMedArticle
5.
Lambert JC, Heath S, Even G,  et al; European Alzheimer's Disease Initiative Investigators.  Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.  Nat Genet. 2009;41(10):1094-1099PubMedArticle
6.
Delcourt C, Delyfer MN, Rougier MB,  et al.  Associations of complement factor H and smoking with early age-related macular degeneration: the ALIENOR study.  Invest Ophthalmol Vis Sci. 2011;52(8):5955-5962PubMedArticle
Research Letters
Aug 2012

ARMS2 A69S Polymorphism and the Risk for Age-Related Maculopathy: The ALIENOR Study

Author Affiliations

Author Affiliations: University of Bordeaux (Drs Delcourt, Delyfer, Colin, Dartigues, and Korobelnik and Ms Le Goff), Inserm, ISPED, Centre Inserm U897–Epidemiologie et Biostatistique (Drs Delcourt, Delyfer, Dartigues, and Korobelnik and Ms Le Goff), and Service d’Ophtalmologie, Centre Hospitalier Universitaire de Bordeaux (Drs Delyfer, Rougier, Colin, Malet, and Korobelnik), Bordeaux, and Inserm, U744, Institut Pasteur de Lille, and Université Lille Nord de France, Lille (Drs Lambert and Amouyel), France.

Arch Ophthalmol. 2012;130(8):1077-1078. doi:10.1001/archophthalmol.2012.420

Since the first evidence of an association of age-related maculopathy (ARM) with a locus on chromosome 10q26 (first named LOC387715, then renamed age-related maculopathy susceptibility 2 [ARMS2 ]) was reported,1,2 many case-control studies have confirmed this finding. However, few data are available from population-based studies, which are less subject to selection bias, and few studies have assessed the association of this polymorphism with early ARM.

In this study, we assessed the associations of ARMS2 A69S genotypes with early and late ARM in the framework of a population-based study of French elderly subjects.

Methods

The ALIENOR (Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires) Study is a population-based epidemiological study on nutrition- and age-related eye diseases.3 It also aims to assess the association of eye diseases with genetic, vascular, and metabolic factors. Between October 2, 2006, and May 23, 2008, 963 residents of Bordeaux, France, aged 73 years or older were recruited among participants of an ongoing cohort study on vascular risk factors for dementia, the 3C Study.

We classified ARM from nonmydriatic 45° color retinal photographs taken using a nonmydriatic retinograph (TRC NW6S; Topcon). Photographs were interpreted according to the international classification4 in double by 2 trained technicians (Delphine Castanet and Hélène Thébault) and adjudicated by a specialist (C.D.) when inconsistent. All cases of late ARM were confirmed by a retina specialist (J.-F.K., M.-B.R., and M.-N.D.). We classified ARM in 5 exclusive stages: none; early ARM1 (large soft distinct drusen without pigment abnormalities or pigment abnormalities without large soft drusen); early ARM2 (large [>125 μm] soft indistinct drusen and/or reticular drusen and/or large distinct drusen with pigment abnormalities); late atrophic ARM (pure geographic atrophy); and late neovascular ARM (serous or hemorrhagic detachment of the retinal pigment epithelium or sensory retina, subretinal or sub–retinal pigment epithelial hemorrhages, and fibrous scar tissue).

The ARMS2 A69S polymorphism (rs10490924) was determined from blood collected between April 15, 1999, and July 7, 2001, in the framework of a genome-wide association study performed in the 3C Study.5 Samples were genotyped with Illumina Human 610-Quad BeadChip (allowing the determination of 537 029 single-nucleotide polymorphisms) and subjected to standard quality control procedures.

Associations were estimated using logistic generalized estimating equations models, subjects without ARM being the reference. Analyses were adjusted for age, sex, complement factor H (CFH) Y402H polymorphism, and smoking—the latter two being other major risk factors for ARM.6

Of 963 subjects, 738 subjects had complete data. There were 1424 gradable eyes.

Results

As shown in the Table, by comparison with the GG genotype, the TT genotype was associated with very high risk for all types of ARM, with increasing odds ratios according to the severity of ARM (from 4.60 for early ARM1 to 23.63 and 16.15 for late atrophic and neovascular ARM, respectively). By contrast, associations of the different types of ARM with the GT genotype were modest (OR, 1.45-2.47) and reached statistical significance only for early ARM1.

Smoking and CFH Y402H remained independently associated with ARM, after controlling for ARMS A69S genotypes (data not shown).

Comment

This population-based study confirms the major contribution of the TT genotype of the ARMS2 A69S polymorphism in early and late ARM, independently from the other 2 major risk factors (smoking and CFH Y402H polymorphism). Associations with the GT genotypes were much weaker, suggesting a moderate codominant genetic mode of action. Strengths of this study include the population-based setting and the photographic assessment and detailed grading of ARM status.

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Article Information

Correspondence: Dr Delcourt, Inserm U897, ISPED, Université Bordeaux Segalen, 146 rue Léo Saignat, Bordeaux 33076, France (cecile.delcourt@isped.u-bordeaux2.fr).

Author Contributions: Ms Le Goff had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: None reported.

Funding/Support: This work was supported by Laboratoires Théa, Clermont-Ferrand, Fondation Voir et Entendre, Paris, and Association Retina France, Colomiers, France.

Role of the Sponsors: Laboratoires Théa participated in the design of the study. No sponsors participated in the conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

References
1.
Rivera A, Fisher SA, Fritsche LG,  et al.  Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk.  Hum Mol Genet. 2005;14(21):3227-3236PubMedArticle
2.
Jakobsdottir J, Conley YP, Weeks DE, Mah TS, Ferrell RE, Gorin MB. Susceptibility genes for age-related maculopathy on chromosome 10q26.  Am J Hum Genet. 2005;77(3):389-407PubMedArticle
3.
Delcourt C, Korobelnik JF, Barberger-Gateau P,  et al.  Nutrition and age-related eye diseases: the ALIENOR (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) Study.  J Nutr Health Aging. 2010;14(10):854-861PubMedArticle
4.
Bird AC, Bressler NM, Bressler SB,  et al; International ARM Epidemiological Study Group.  An international classification and grading system for age-related maculopathy and age-related macular degeneration.  Surv Ophthalmol. 1995;39(5):367-374PubMedArticle
5.
Lambert JC, Heath S, Even G,  et al; European Alzheimer's Disease Initiative Investigators.  Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.  Nat Genet. 2009;41(10):1094-1099PubMedArticle
6.
Delcourt C, Delyfer MN, Rougier MB,  et al.  Associations of complement factor H and smoking with early age-related macular degeneration: the ALIENOR study.  Invest Ophthalmol Vis Sci. 2011;52(8):5955-5962PubMedArticle
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