Genotypic influences on severity of exudative age-related macular degeneration

Major genetic risk factors have recently been identified for age-related macular degeneration (AMD), including the ARMS2/LOC387715 and CFH at-risk polymorphisms. The study was conducted to establish correlations between the AMD genotype and both the phenotype and severity of AMD. In a prospective co...

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Bibliographic Details
Published in:Investigative ophthalmology & visual science 2010-05, Vol.51 (5), p.2620-2625
Main Authors: Leveziel, Nicolas, Puche, Nathalie, Richard, Florence, Somner, John E A, Zerbib, Jennyfer, Bastuji-Garin, Sylvie, Cohen, Salomon Y, Korobelnik, Jean-François, Sahel, José, Soubrane, Gisèle, Benlian, Pascale, Souied, Eric H
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Alleles
Complement Factor H - genetics
Exudates and Transudates
Female
Fluorescein Angiography
Genotype
Humans
Macular Degeneration - genetics
Male
Phenotype
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Prospective Studies
Proteins - genetics
Severity of Illness Index
Visual Acuity
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Summary:Major genetic risk factors have recently been identified for age-related macular degeneration (AMD), including the ARMS2/LOC387715 and CFH at-risk polymorphisms. The study was conducted to establish correlations between the AMD genotype and both the phenotype and severity of AMD. In a prospective cohort of 1216 AMD patients, four genotypic homozygous groups were identified (n = 264): double homozygous for wild-type alleles (group 1, n = 49), homozygous for the at-risk allele of ARMS2/LOC387715 only (group 2, n = 57), homozygous for the at-risk allele of CFH only (group 3, n = 106), and double homozygous for both at-risk alleles (group 4, n = 52). The phenotypic classification of exudative AMD was based on fluorescein angiography. Mean age at presentation was significantly lower in group 4 than in group 1 (P < 0.014). Patients in group 4 presented more often with bilateral CNV and fibrovascular scars than did patients in group 1 (P < 0.001 and < 0.0031 respectively) and with significantly lower visual acuity (VA) in the first affected eye than did patients in group 1 (P < 0.02). Patients in group 2 presented with worse VA than did patients in group 3 (P < 0.003). Classic CNV was more commonly associated with the at-risk allele of the ARMS2/LOC387715 locus than with the at-risk allele of the CFH gene (P < 0.026). This study demonstrates an association between the at-risk allele of the ARMS2/LOC387715 locus and classic CNV, fibrovascular lesions, and poor VA. Individuals double homozygous for both at-risk alleles had a higher risk of being affected with a severe form of AMD at an earlier age.
ISSN:1552-5783
1552-5783
DOI:10.1167/iovs.09-4423