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Stephanie A. Hagstrom, Gui-Shuang Ying, Gayle J. Pauer, Gwen M. Sturgill-Short, Jiayan Huang, Maureen G. Maguire, Daniel F. Martin, CATT Research Group; Pharmacogenetics of Anti-VEGF Therapy in the Comparison of AMD Treatments Trials (CATT). Invest. Ophthalmol. Vis. Sci. 2012;53(14):3682.
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To evaluate the pharmacogenetic relationship between genotypes of single nucleotide polymorphisms (SNPs) known to be associated with age-related macular degeneration (AMD) and response to treatment with ranibizumab or bevacizumab for neovascular AMD.
834 (75%) of 1116 patients participating in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 CATT clinical centers. Each patient was genotyped for SNPs rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3), using TaqMan SNP genotyping assays. Genotypic frequencies were compared to clinical measures of response to therapy at one year including visual acuity (VA), change in VA, presence of fluid, retinal thickness, change in lesion size and number of injections in the as needed groups. Differences in response by genotype were evaluated with chi-square statistics for categorical outcomes and by ANOVA for continuous outcomes.
The genotypic frequencies for each SNP analyzed were balanced across treatment groups. The frequency of high-risk alleles among CATT participants was higher than in the general population. No statistically significant differences (p≤0.01) in response by genotype were identified for any of the clinical measures studied. Specifically, there were no high-risk alleles that predicted final VA or change in VA, the degree of anatomical response (fluid on OCT, retinal thickness or change in lesion size) or number of injections. Furthermore, a stepwise analysis failed to show a significant epistatic interaction among the variants analyzed; ie, response did not vary by the number of risk alleles present. The results did not differ by the drug used for treatment.
Although specific alleles for CFH, ARMS2, HTRA1 and C3 may predict the development of AMD, there was no evidence that they predict response to anti-VEGF therapy.
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