PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
PURPOSE: 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. METHODS: In a prospective cohort of 1216 AMDpatients, 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: Lucia Sobrin; Robyn Reynolds; Yi Yu; Jesen Fagerness; Nicolas Leveziel; Paul S Bernstein; Eric H Souied; Mark J Daly; Johanna M Seddon Journal: Am J Ophthalmol Date: 2010-12-03 Impact factor: 5.258
Authors: R Theodore Smith; Joanna E Merriam; Mahsa A Sohrab; Nicole M Pumariega; Gaetano Barile; Anna M Blonska; Raymond Haans; David Madigan; Rando Allikmets Journal: Arch Ophthalmol Date: 2011-08
Authors: Stephen G Schwartz; Anita Agarwal; Jaclyn L Kovach; Paul J Gallins; William Cade; Eric A Postel; Gaofeng Wang; Juan Ayala-Haedo; Kylee M Spencer; Jonathan L Haines; Margaret A Pericak-Vance; William K Scott Journal: Retina Date: 2012-09 Impact factor: 4.256
Authors: Maureen G Maguire; Gui-Shuang Ying; Glenn J Jaffe; Cynthia A Toth; Ebenezer Daniel; Juan Grunwald; Daniel F Martin; Stephanie A Hagstrom Journal: JAMA Ophthalmol Date: 2016-06-01 Impact factor: 7.389