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Genotype Determination

Pharmacogenetics for Genes Associated with Age-Related M acular Degeneration in the Comparison of AMD Treatments Trials (CATT). Hagstrom SA, Ying G-S, Pauer GJT, Sturgill -Short GM, Huang J, Callanan DG, Kim IK, Klein ML, Maguire MG , Martin DF for the CATT Research Group

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Genotype Determination

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  1. Pharmacogenetics for Genes Associated with Age-Related Macular Degeneration in the Comparison of AMD Treatments Trials (CATT) Hagstrom SA, Ying G-S, Pauer GJT, Sturgill-Short GM, Huang J, Callanan DG, Kim IK, Klein ML, Maguire MG, Martin DF for the CATT Research Group Available through http://www.med.upenn.edu/cpob/publications_main.shtml Supported by Cooperative Agreements from the National Eye Institute, National Institutes of Health, DHHS 1

  2. Genotype Determination Inflammation Lipid Metabolism CFH C3 C2 CFI BF APOE LIPC CETP LPL ABCA1 AMD Biological Pathways Angiogenesis ECM Stasis VEGFA KDR HTRA1 TIMP3 COL8A1 FRK Oxidative Stress ARMS2 ND2 Each patient was genotyped for CFH, ARMS2, HTRA1, and C3. Hagstrom et al. Pharmacogenetics of Anti-VEGF Therapy in CATT Ophthalmology 2013;120:593-599

  3. Genotype Determination Genotyping was performed using a custom made TaqManOpenArray loaded with TaqMan SNP genotyping assays. Homozygous Allele 1 Heterozygous Homozygous Allele 2 Negative Controls Hagstrom et al. Pharmacogenetics of Anti-VEGF Therapy in CATT Ophthalmology 2013;120:593-599

  4. Outcome Variables All outcomes were determined following standardized protocols. VA assessed using eETDRS testing OCT outcomes determined by independent OCT Reading Center FA and photographic outcomes determined by independent Fundus Photographic Reading Center Hagstrom et al. Pharmacogenetics of Anti-VEGF Therapy in CATT Ophthalmology 2013;120:593-599

  5. Comparison of baseline demographic and ocular characteristics between participants and non-participants in the genetic study (N=1149) SD = standard deviation; AREDS = age-related eye disease study; VA = visual acuity; DA = disc area. Hagstrom et al. Pharmacogenetics of Anti-VEGF Therapy in CATT Ophthalmology 2013;120:593-599

  6. Visual Outcomes by Genotype 6

  7. Genotypic Associations with Anatomic Outcome Measures on OCT at 1 Year (N=834) Hagstrom et al. Pharmacogenetics of Anti-VEGF Therapy in CATT Ophthalmology 2013;120:593-599 7

  8. FA and Fundus Outcomes by Genotype (N=834) Hagstrom et al. Pharmacogenetics of Anti-VEGF Therapy in CATT Ophthalmology 2013;120:593-599 8

  9. Number of Injections by Genotype Hagstrom et al. Pharmacogenetics of Anti-VEGF Therapy in CATT Ophthalmology 2013;120:593-599 9

  10. Conclusions Largest pharmacogenetic analysis exploring the relationship between genotypes and response to anti-VEGF therapy with >90% power to detect a 1 line difference between the highest risk and lowest risk groups. The relationship between genotype and response to therapy did not vary by drug or dosing regimen. Although specific risk alleles for CFH, ARMS2, HTRA1 and C3 may predict the development of AMD, they did not predict response to anti-VEGF therapy. Further studies targeting SNPs in additional biological pathways are ongoing. Hagstrom et al. Pharmacogenetics of Anti-VEGF Therapy in CATT Ophthalmology 2013;120:593-599 10

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