Interleukin 8 promoter polymorphism predicts the initial response to bevacizumab treatment for exudative age-related macular degeneration

Retina. 2013 Oct;33(9):1815-27. doi: 10.1097/IAE.0b013e318285cf92.

Abstract

Purpose: 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.

Conclusion: The A allele and the homozygous AA genotype of interleukin 8 -251A/T were associated with anatomical nonresponse to bevacizumab treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bevacizumab
  • Complement C3 / genetics
  • Complement Factor H / genetics
  • Exudates and Transudates
  • Female
  • Genotype
  • Humans
  • Interleukin-8 / genetics*
  • Intravitreal Injections
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic / genetics*
  • Prospective Studies
  • Proteins / genetics
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics
  • Visual Acuity / physiology
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / genetics*

Substances

  • ARMS2 protein, human
  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • CFH protein, human
  • CXCL8 protein, human
  • Complement C3
  • Interleukin-8
  • Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Complement Factor H