title: VEGFA and VEGFR2 gene polymorphisms and response to anti-vascular endothelial growth factor therapy: comparison of age-related macular degeneration treatments trials (CATT).
abstract: OBJECTIVE
  Individual variation in response and duration of anti-vascular endothelial growth factor (VEGF) therapy is seen among patients with neovascular age-related macular degeneration. Identification of genetic markers that affect clinical response may result in optimization of anti-VEGF therapy.
  
  
  OBJECTIVE
  To evaluate the pharmacogenetic relationship between genotypes of single-nucleotide polymorphisms (SNPs) in the VEGF signaling pathway and response to treatment with ranibizumab or bevacizumab for neovascular age-related macular degeneration.
  
  
  METHODS
  In total, 835 of 1149 patients (72.7%) participating in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) at 43 CATT clinical centers.
  
  
  METHODS
  Each patient was genotyped for 7 SNPs in VEGFA (rs699946, rs699947, rs833069, rs833070, rs1413711, rs2010963, and rs2146323) and 1 SNP in VEGFR2 (rs2071559) using TaqMan SNP genotyping assays.
  
  
  METHODS
  Genotypic frequencies were compared with clinical measures of response to therapy at 1 year, including the mean visual acuity, mean change in visual acuity, at least a 15-letter increase, retinal thickness, mean change in total foveal thickness, presence of fluid on optical coherence tomography, presence of leakage on fluorescein angiography, 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. The method of controlling the false discovery rate was used to adjust for multiple comparisons.
  
  
  RESULTS
  For each of the measures of visual acuity evaluated, no association was observed with any of the genotypes or with the number of risk alleles. Four VEGFA SNPs demonstrated an association with retinal thickness: rs699947 (P = .03), rs833070 (P = .04), rs1413711 (P = .045), and rs2146323 (P = .006). However, adjusted P values for these associations were all statistically nonsignificant (range, P = .24 to P = .45). Among the participants in 2 as-needed groups, no association was found in the number of injections among the different genotypes or for the total number of risk alleles. The effect of risk alleles on each clinical measure did not differ by treatment group, drug, or dosing regimen (P > .01 for all).
  
  
  CONCLUSIONS
  This study provides evidence that no pharmacogenetic associations exist between the studied VEGFA and VEGFR2 SNPs and response to anti-VEGF therapy.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00593450.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Hagstrom
authors.forename: Gui-shuang
authors.initials: GS
authors.lastname: Ying
authors.forename: Gayle J T
authors.initials: GJ
authors.lastname: Pauer
authors.forename: Gwen M
authors.initials: GM
authors.lastname: Sturgill-Short
authors.forename: Jiayan
authors.initials: J
authors.lastname: Huang
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Maguire
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Martin
mesh_terms: D000368:Aged; D000483:Alleles; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D004247:DNA / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic / Q000187:drug effects*; D000069579:Ranibizumab; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D015398:Signal Transduction; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D004247:DNA; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D000069579:Ranibizumab