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

VEGFR2 gene polymorphisms and response to anti-vascular endothelial growth factor therapy in age-related macular degeneration
VEGFR2 gene polymorphisms and response to anti-vascular endothelial growth factor therapy in age-related macular degeneration
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.
1563-1568
Hagstrom, Stephanie A.
b5dd5c35-510b-4230-985c-15a972a6fec7
Ying, Gui-shuang
09efdae7-b0a7-4e7e-8e57-8b1fc674f13a
Maguire, Maureen G.
3b7f4f40-63d4-414d-8134-f472a86974e0
Martin, Daniel F.
251f3bca-6b2c-416e-9bb9-988ca9316395
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Gibson, Jane
855033a6-38f3-4853-8f60-d7d4561226ae
Chakravarthy, Usha
2c06cdaf-94c0-409a-8eff-2f624c120a5e
CATT Research Group, [Unknown]
e7a60188-b1a1-4e96-8f5c-3b2d255ef19e
IVAN Study Group, [Unknown]
c53961ba-0a3b-4e84-a68d-93351617cbca
Hagstrom, Stephanie A.
b5dd5c35-510b-4230-985c-15a972a6fec7
Ying, Gui-shuang
09efdae7-b0a7-4e7e-8e57-8b1fc674f13a
Maguire, Maureen G.
3b7f4f40-63d4-414d-8134-f472a86974e0
Martin, Daniel F.
251f3bca-6b2c-416e-9bb9-988ca9316395
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Gibson, Jane
855033a6-38f3-4853-8f60-d7d4561226ae
Chakravarthy, Usha
2c06cdaf-94c0-409a-8eff-2f624c120a5e
CATT Research Group, [Unknown]
e7a60188-b1a1-4e96-8f5c-3b2d255ef19e
IVAN Study Group, [Unknown]
c53961ba-0a3b-4e84-a68d-93351617cbca

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)

Record type: Article

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.

Full text not available from this repository.

More information

Accepted/In Press date: 21 April 2015
e-pub ahead of print date: 28 May 2015
Published date: 8 August 2015
Organisations: Molecular and Cellular, Faculty of Medicine

Identifiers

Local EPrints ID: 390415
URI: http://eprints.soton.ac.uk/id/eprint/390415
PURE UUID: e5d2de79-f1e5-4cf8-8a2b-07f1418a0503
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305
ORCID for Jane Gibson: ORCID iD orcid.org/0000-0002-0973-8285

Catalogue record

Date deposited: 01 Apr 2016 11:27
Last modified: 18 Feb 2021 17:01

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