Abstract
Purpose:
To evaluate the pharmacogenetic relationship of genotypes of single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor (VEGF-A) and its main receptor (VEGFR-2) with response to intravitreal injections of ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD).
Methods:
835 (75%) of 1116 patients participating in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 CATT clinical centers. Each patient was genotyped for seven SNPs in VEGF-A (rs699946, rs699947, rs833069, rs833070, rs1413711, rs2010963, rs2146323) and one SNP in the high-affinity VEGF-A receptor, VEGFR-2 (rs2071559), using TaqMan SNP genotyping assays. Genotypic frequencies were compared to clinical measures of response to therapy at one year including visual acuity (VA), change in VA, presence of fluid, retinal thickness, change in lesion size and number of injections in the as needed groups. Differences in response by genotype were evaluated with tests of linear trend calculated from logistic regression models for categorical outcomes and linear regression models for continuous outcomes. A stepwise analysis was performed to examine the additive effects based upon the total number of risk alleles from the eight SNPs.
Results:
The genotypic frequencies for each SNP analyzed were balanced across treatment groups. The effect of risk alleles on each clinical measure did not differ by treatment group, drug or dosing regimen (p >0.01). Therefore, we collapsed all treatment groups and report our findings on the entire 835 patients as a single group. For each of the measures of VA evaluated, there was no association with any of the genotypes or with the number of risk alleles from the eight SNPs. Four of the VEGF-A SNPs demonstrated an association with retinal thickness (rs699947, rs833070, rs1413711, p=0.03 to 0.04; rs2146323, p=0.006). However, none of these modest associations were supported by any other anatomical measure. Among the participants in the two PRN groups, no association was found in the number of injections among the different genotypes for any of the eight SNPs, or for the total number of risk alleles from the eight SNPs.
Conclusions:
There were no strong pharmacogenetic associations between the studied VEGF-A and VEGFR-2 SNPs and response to anti-VEGF therapy in patients participating in CATT.
Keywords: 539 genetics •
412 age-related macular degeneration