title: Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT).
abstract: OBJECTIVE
  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 (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech) for neovascular AMD.
  
  
  METHODS
  Clinical trial.
  
  
  METHODS
  Eight hundred thirty-four (73%) of 1149 patients participating in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 CATT clinical centers.
  
  
  METHODS
  Each patient was genotyped for SNPs rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3), using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA).
  
  
  METHODS
  Genotypic frequencies were compared with clinical measures of response to therapy at one year, including mean visual acuity (VA), mean change in VA, 15-letter or more increase in VA, retinal thickness, mean change in total foveal thickness, presence of fluid on OCT, presence of leakage on fluorescein angiography (FA), mean change in lesion size, and mean number of injections administered. Differences in response by genotype were evaluated with tests of linear trend calculated from logistic regression models for categorical outcomes and linear regression models for continuous outcomes. To adjust for multiple comparisons, P≤0.01 was considered statistically significant.
  
  
  RESULTS
  No statistically significant differences 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 anatomic response (fluid on OCT or FA, retinal thickness, change in total foveal thickness, change in lesion size), or the number of injections. Furthermore, a stepwise analysis failed to show a significant epistatic interaction among the variants analyzed; that is, response did not vary by the number of risk alleles present. The lack of association was similar whether patients were treated with ranibizumab or bevacizumab or whether they received monthly or pro re nata dosing.
  
  
  CONCLUSIONS
  Although specific alleles for CFH, ARMS2, HTRA1, and C3 may predict the development of AMD, they did not predict response to anti-vascular endothelial growth factor therapy.
authors: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. Electronic address: hagstrs@ccf.org.
authors: Stephanie A
authors: SA
authors: Hagstrom
authors: Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Gui-Shuang
authors: GS
authors: Ying
authors: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Gayle J T
authors: GJT
authors: Pauer
authors: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Gwen M
authors: GM
authors: Sturgill-Short
authors: Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Jiayan
authors: J
authors: Huang
authors: Texas Retina Associates, Arlington, Texas.
authors: David G
authors: DG
authors: Callanan
authors: Retina Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors: Ivana K
authors: IK
authors: Kim
authors: Casey Eye Institute, Oregon Health Sciences Center, Portland, Oregon.
authors: Michael L
authors: ML
authors: Klein
authors: Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Maureen G
authors: MG
authors: Maguire
authors: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Daniel F
authors: DF
authors: Martin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D003176:Complement C3 / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005787:Gene Frequency; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D000069579:Ranibizumab; D012697:Serine Endopeptidases / Q000235:genetics*; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology
chemical_list: C514392:ARMS2 protein, human; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C493495:CFH protein, human; D003176:Complement C3; D011506:Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D000069579:Ranibizumab