Vascular Endothelial Growth Factor Polymorphism and the Response to Intravitreal Bevacizumab in Age-Related Macular Degeneration

Abstract

Purpose: : To investigate the association between single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor (VEGF) gene and response to intravitreal bevacizumab (IVB) for neovascular age-related macular degeneration (AMD).

Methods: : In this retrospective study, a total of 94 patients with neovascular AMD were treated with IVB as the first treatment, and an intravitreal anti-VEGF drug (bevacizumab or pegaptanib or ranibizumab) was given when recurrence occurred. Genomic DNAs were prepared from peripheral blood and the genotyping was performed using the Taqman SNP assay. Genotypes were determined for the 4 selected tagging SNPs across the VEGF gene. Visual acuity (VA) before and after treatment, number of treatments, frequency of recurrence, and the period until the recurrence were retrospectively evaluated.

Results: : Of the 4 SNPs studied, one SNP (rs699946) was significantly associated with the visual prognosis after the treatment. The genotypes of the rs699946 SNP in the study sample were AA in 24.2% (22/91), CT in 51.6% (47/91), and TT in 24.2% (22/91). There was no significant difference in the mean baseline VA among these three genotypes of rs699946 (P = 0.101). After treatment, however, mean VA continuously improved in the rs699946 GG genotype patients, whereas the mean VA did not change notably during the follow-up period in the AG and AA genotype patients. Seventy-five patients were followed up for more than 1 year after the first treatment, and we found significant difference in the mean VA at 12 months among these three genotypes (P = 0.025). Furthermore, when we examined changes in visual acuity among the three genotypes, the G allele showed a significant trend toward better VA change (P = 0.044). There were no significant differences in the number of treatments, frequency of recurrence and the period until the recurrence according to VEGF genetic variants.

Conclusions: : In the present study, VA outcome after anti-VEGF treatment for neovascular AMD differed according to VEGF genotype. The VEGF genetic variant would affect the reactivity of neovascular AMD to anti-VEGF drugs.

Keywords: age-related macular degeneration • genetics • vascular endothelial growth factor