VEGFR2 Gene Polymorphisms and Response to Anti–Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration
Open accessAbstract
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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Two large, multicenter randomized clinical trials could not replicate the reported pharmacogenetic associations with anti-VEGF treatment.
“However, two large, multicenter randomized clinical trials could not replicate these findings [36,37].”
From Genetics and Age-Related Macular Degeneration: A Practical Review for Clinicians. (2024) · cites this paper as [37]
Data in IVAN and CATT randomized controlled trials did not support a pharmacogenetic association between the two VEGFR2 SNPs, rs4576072 and rs6828477, and response to anti-VEGF therapy.
“Also, data in the Inhibition of VEGF in Age-Related Choroidal Neovascularization (IVAN) and CATT randomized controlled trials did not support a pharmacogenetic association between the two VEGFR2 SNPs, rs4576072 and rs6828477, and response to anti-VEGF therapy.25”
From <i>ANO2</i> Genetic Variants and Anti-VEGF Treatment Response in Neovascular AMD: A Pharmacogenetic Substudy of VIEW 1 and VIEW 2 (2024) · cites this paper as [25]
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References 12 · Cited by 37
- Authors
- Hagstrom, S. A., Ying, G.-S., Maguire, M. G., Martin, D. F., Gibson, J., Lotery, A., & Chakravarthy, U.
- Affiliations
- Cleveland Clinic (US)
- University of Pennsylvania (US)
- University of Southampton (GB)
- Queen's University Belfast (GB)
- Corresponding author
- Hagstrom, Stephanie A.
- ORCID
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 122
- Issue
- 8
- Pages
- 1563-1568
- ISSN
- 0161-6420 (ISSN-L)
- PMC
- PMC4516643
- OpenAlex
- W1650810542
- Cited by
- 37
- References
- 12
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 4
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- National Eye Institute (U10EY017825, U10EY017826, R21EY023689, U10EY017823, U10EY017828)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- VEGFR2, single nucleotide polymorphisms, pharmacogenetics, anti-VEGF therapy, ranibizumab, bevacizumab, neovascular age-related macular degeneration, choroidal neovascularization, treatment response prediction
- MeSH terms
- Ranibizumab, Aged, Aged, 80 and over, Female, Gene Frequency, Humans, Male, Middle Aged, Pharmacogenetics, Visual Acuity, Angiogenesis Inhibitors, Polymorphism, Single Nucleotide, Vascular Endothelial Growth Factor Receptor-2, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A, Wet Macular Degeneration, Intravitreal Injections, Genotyping Techniques, Antibodies, Monoclonal, Humanized
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