title: CFH, VEGF and HTRA1 promoter genotype may influence the response to intravitreal ranibizumab therapy for neovascular age-related macular degeneration.
abstract: OBJECTIVE
  To investigate an association between genotype for three single nucleotide polymorphisms strongly associated with the development of age-related macular degeneration (AMD) and the early response to treatment with intravitreal ranibizumab for neovascular AMD.
  
  
  METHODS
  Best corrected visual acuity letter score was recorded at baseline and each subsequent visit. Age, sex, smoking history, lesion type and the number of injections were also recorded. Genotypes were obtained for rs11200638 in HTRA1, rs1061170 in CFH and rs1413711 in VEGF. Data were analysed with treatment response at month 6 as both a binary (>5 letter improvement vs ≤5 letter gain) and a linear trait.
  
  
  RESULTS
  This initial study cohort consisted of 104 Caucasian neovascular AMD patients treated with intravitreal ranibizumab. Trends towards a more favourable outcome were seen with the higher AMD risk genotypes in CFH and VEGF in both the linear and binary models and in HTRA1 in the linear model alone. For CFH, mean letter score change after 6 months was +1.6, +5.9 and +7.2 letters for the TT, TC and CC genotypes and a >5 letter gain was seen in 34.6%, 56.6% and 56%, respectively. For VEGF, mean letter score change after 6 months was +1.3, +5.8 and +7.4 letters for the TT, TC and CC genotypes and a >5 letter gain was seen in 40%, 55.8% and 51.9%, respectively. For HTRA1, mean letter score change was +2.2, +7.5 and +2.9 letters for the GG, GA and AA genotypes.
  
  
  CONCLUSIONS
  This study reports preliminary evidence suggesting that the higher AMD risk genotypes in CFH, VEGF and HTRA1 may influence the short-term response to treatment with ranibizumab for neovascular AMD.
authors.affiliation: Eye Clinic, St James's University Hospital, Leeds LS9 7TF, UK. martin.mckibbin@leedsth.nhs.uk
authors.forename: Martin
authors.initials: M
authors.lastname: McKibbin
authors.forename: Manir
authors.initials: M
authors.lastname: Ali
authors.forename: Shveta
authors.initials: S
authors.lastname: Bansal
authors.forename: Paul D
authors.initials: PD
authors.lastname: Baxter
authors.forename: Kumi
authors.initials: K
authors.lastname: West
authors.forename: Grange
authors.initials: G
authors.lastname: Williams
authors.forename: Frances
authors.initials: F
authors.lastname: Cassidy
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007208:Indocyanine Green; D058449:Intravitreal Injections; D008297:Male; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000069579:Ranibizumab; D012697:Serine Endopeptidases / Q000235:genetics*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C493495:CFH protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D007208:Indocyanine Green; D000069579:Ranibizumab