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Maureen G Maguire, Stephanie A Hagstrom, Gui-Shuang Ying, ; Influence of SNPs Associated with Age-related Macular Degeneration (AMD) on the Phenotype of Neovascular Lesions in the Comparison of AMD Treatments Trials (CATT). Invest. Ophthalmol. Vis. Sci. 2014;55(13):865.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the influence of genotypes of single nucleotide polymorphisms (SNPs) known to be associated with age-related macular degeneration (AMD) on the phenotype of neovascular lesions.
834 (75%) of 1149 subjects in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 clinical centers. Each subject was genotyped for SNPs rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3), using TaqMan SNP genotyping assays. Genotypic frequencies were compared to pre-treatment ocular characteristics on fluorescein angiography (lesion type, area of neovascularization and total lesion, retinal angiomatous proliferation (RAP)), and on time-domain optical coherence tomography (presence of intraretinal, subretinal and sub-RPE fluid; thickness at the foveal center of the retina, subretinal fluid, and subretinal tissue complex) and to visual acuity and age. The association between the phenotype and the number of risk alleles (0,1,2) for each genotype was evaluated using logistic regression models for categorical characteristics and linear regression models for continuous characteristics. Nominal linear trend p-values, without correction for multiple comparisons, are presented.
Mean age decreased with the number of risk alleles for each SNP (p<0.05). Mean area of the total lesion increased with the number of risk alleles for ARMS2 as well as for the sum of risk alleles for all 4 SNPs, from 2.0mm2 with 0 or 1 risk allele to 2.7mm2 with ≥4 risk alleles (p=0.003). The proportion with RAP lesions decreased with the number of risk alleles for CFH with 13%, 11%, and 6% for 0, 1, and 2 risk alleles, respectively (p=0.02). For C3, the proportions with intraretinal fluid (p<0.001) and with abnormally thick retinas (p<0.02) decreased with higher numbers of risk alleles. The proportion with intraretinal fluid increased with higher numbers of risk alleles for ARMS2 (73% for 0 risk alleles and 84% for 2 risk alleles; p=0.02) and for HTRA1 (72% for 0 risk alleles and 84% for 2 risk alleles; p=0.04).
CFH, ARMS2, HTRA1 and C3 were each associated with specific features of eyes with neovascularization within CATT. Previously identified associations of ARMS2 and CFH with CNV type were not confirmed. New associations identified in CATT need confirmation before assuming a true association exists.
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