Effect of Risk Alleles in CFH, C3, and VEGFA on the Response to Intravitreal Bevacizumab in Tunisian patients with neovascular AMD

Abstract

Purpose: The aim of this pharmacogenetic study was to evaluate the impact of high-risk alleles in CFH, C3 and VEGF on the response to intravitreal bevacizumab in Tunisian patients with neovascular age-related macular degeneration.

Methods: Ninety patients with active neovascular AMD treated with intravitreal bevacizumab injections were enrolled in this study. Treatment response was evaluated by comparing BCVA at baseline and at 12 months. Patients were classified into either “poor responders” (PR) (loss of 2 lines or more) and “good responders” (GR) (gain of less than 2 lines). Single nucleotide polymorphism (SNP) genotyping (Y402H) of FH, (+405) C/G, (+936) C/T, (-2578) C/A of VEGF and (R102G) of C3 was performed. The association between genotype and visual response at 12 months was assessed.

Results: Among the 90 participants, 77 were assigned to the GR group and 13 to the PR group. No difference was shown in FH and C3 variant alleles with treatment response. However, patient with genotype GG of (+405) G/C in VEGF and those with genotype AA of (-2578) C/A in VEGF were significantly associated with poor treatment response (p=0,024 and p=0,049 respectively). In fact, haplotype analysis of (+936) (C/T), (+405) (C/G) and (-2578) (C/A) SNPs of VEGF revealed that TGA haplotype was associated with a PR (p=0.048).

Conclusions: Genetic predisposition may play a role in the variability of the response to anti-VEGF therapy. The VEGF haplotype TGA can thus be applied as a marker for poor visual prognosis in patients with neovascular AMD treated with Bevacizumab.

Keywords: 412 age-related macular degeneration • 748 vascular endothelial growth factor • 440 candidate gene analysis