VEGFR2 gene polymorphisms and response to anti-vascular endothelial growth factor therapy in age-related macular degeneration

Hagstrom, Stephanie A., Ying, Gui-shuang, Maguire, Maureen G., Martin, Daniel F., Lotery, Andrew, Gibson, Jane, Chakravarthy, Usha, CATT Research Group, [Unknown] and IVAN Study Group, [Unknown] (2015) VEGFR2 gene polymorphisms and response to anti-vascular endothelial growth factor therapy in age-related macular degeneration. Ophthalmology, 122 (8), 1563-1568. (doi:10.1016/j.ophtha.2015.04.024). (PMID:22578446)

Abstract

Purpose: A previously published study demonstrated a pharmacogenetic association between the minor alleles of 2 VEGFR2 single nucleotide polymorphisms (SNPs) and greater improvement in visual acuity (VA) to treatment with ranibizumab, an anti–vascular endothelial growth factor (VEGF) drug, in patients with neovascular age-related macular degeneration (AMD). We evaluated whether this association was replicated among patients who participated in the Comparison of AMD Treatments Trials (CATT) or the Alternative Treatments to Inhibit VEGF in Patients with Age-Related Choroidal Neovascularisation (IVAN) trial.

Design: Cohort studies within randomized clinical trials.

Participants: Eight hundred thirty-five patients participating in CATT and 512 patients participating in IVAN.

Methods: Each patient was genotyped for the SNPs rs4576072 and rs6828477 in the VEGFR2 gene.

Main Outcomes Measures: Mean change in VA from baseline to 1 year after initiation of treatment with ranibizumab or bevacizumab. Differences in VA response between the patient group homozygous for the minor allele of each SNP and the other genotype groups were evaluated with analysis of variance. Differences in VA response by the number of minor alleles present for either SNP or both combined were evaluated with tests of linear trend. Analyses were conducted separately for CATT and IVAN participants and with both the studies combined.

Results: No statistically significant difference in mean change in VA was identified between genotypes of either SNP (P ? 0.05). Furthermore, a stepwise analysis failed to show a significant interaction for either SNP based on the number of minor alleles present. The lack of association was similar in both the CATT and IVAN cohorts and whether the analysis combined patients treated with either ranibizumab or bevacizumab or when restricted to patients treated with ranibizumab only.

Conclusions: The CATT and IVAN data do not support a pharmacogenetic association between the 2 VEGFR2 SNPs, rs4576072 and rs6828477, and change in VA in response to anti-VEGF therapy in patients with neovascular AMD.

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Contributors

Author: Andrew Lotery

Author: Jane Gibson

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