title: Interleukin 8 promoter polymorphism predicts the initial response to bevacizumab treatment for exudative age-related macular degeneration.
abstract: OBJECTIVE
  To study the association of single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes with the response to bevacizumab treatment in exudative age-related macular degeneration.
  
  
  METHODS
  Clinical records, smoking history, optical coherence tomography, and angiographies of 96 bevacizumab-treated exudative age-related macular degeneration patients were analyzed retrospectively. Blood DNA was collected. Based on the disappearance of intra- or subretinal fluid in optical coherence tomography, patients were graded as responders, partial responders, or nonresponders after 3 initial treatment visits and a median time of 3.5 months.
  
  
  RESULTS
  Interleukin 8 promoter polymorphism -251A/T was significantly associated with persisting fluid in optical coherence tomography. The A allele was more frequent in nonresponders than in responders (P = 0.033). In multivariate modeling, the AA genotype of -251A/T (P = 0.043) and occult (P = 0.042) or predominantly classic (P = 0.040) lesions predicted poorer outcome. Visual acuity change was better in responders than in nonresponders (P = 0.006). Baseline lesion size (P = 0.006) and retinal cysts after the treatment (P < 0.001) correlated with less visual acuity gain.
  
  
  CONCLUSIONS
  The A allele and the homozygous AA genotype of interleukin 8 -251A/T were associated with anatomical nonresponse to bevacizumab treatment.
authors.affiliation: *Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland †Department of Medical Genetics, University of Helsinki, Helsinki, Finland Departments of ‡Ophthalmology, Institute of Clinical Medicine, and §Internal Medicine, Clinical Research Center and Biocenter Oulu, University of Oulu, Oulu, Finland ¶Department of Clinical Chemistry, Oulu University Hospital, Oulu, Finland **Department of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Asta
authors.initials: A
authors.lastname: Hautamäki
authors.forename: Jarno
authors.initials: J
authors.lastname: Kivioja
authors.forename: Satu
authors.initials: S
authors.lastname: Vavuli
authors.forename: Sakari
authors.initials: S
authors.lastname: Kakko
authors.forename: Eeva-Riitta
authors.initials: ER
authors.lastname: Savolainen
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Savolainen
authors.forename: M Johanna
authors.initials: MJ
authors.lastname: Liinamaa
authors.forename: Sanna
authors.initials: S
authors.lastname: Seitsonen
authors.forename: Päivi
authors.initials: P
authors.lastname: Onkamo
authors.forename: Irma
authors.initials: I
authors.lastname: Järvelä
authors.forename: Ilkka
authors.initials: I
authors.lastname: Immonen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; 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; D005122:Exudates and Transudates; D005260:Female; D005838:Genotype; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C493495:CFH protein, human; C508606:CXCL8 protein, human; D003176:Complement C3; D016209:Interleukin-8; D011506:Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D017242:Complement Factor H