VEGF-A polymorphisms predict short-term functional response to intravitreal ranibizumab in exudative age-related macular degeneration

Pharmacogenomics. 2013 Apr;14(6):623-30. doi: 10.2217/pgs.13.43.

Abstract

Aim: To investigate the association between VEGF gene SNPs and early response to intravitreal ranibizumab for exudative age-related macular degeneration.

Materials & methods: Sixty-four patients (64 eyes) were prospectively enrolled and treated for neovascular age-related macular degeneration with ranibizumab monotherapy. Visual acuity was measured using the ETDRS chart. A loading phase of 3 monthly intravitreal injections of ranibizumab 0.5 mg/0.05 ml was performed. The analyzed VEGF-A gene SNPs were rs699947 (-2578A/C) and rs1570360 (-1154G/A); the allelic discrimination was performed in real-time PCR platform. The difference of best corrected visual acuity (ETDRS letters) read before and after treatment was considered as functional outcome.

Results: Ranibizumab was significantly more effective as measured by best corrected visual acuity in patients harboring the VEGF-A -2578C allele (from +6.26 to +7.44 ETDRS letters), whereas patients carrying the VEGF-A -2578AA genotype revealed an absence of early functional response to ranibizumab (-1.78 ETDRS letters; p = 0.0192).

Conclusion: This study suggests that the VEGF-A -2578A/C SNP may represent an important molecular determinant of the early functional outcome of ranibizumab. Original submitted 3 December 2012; Revision submitted 18 February 2013.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Female
  • Genotype
  • Humans
  • Intravitreal Injections / methods
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Ranibizumab
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Antibodies, Monoclonal, Humanized
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Ranibizumab