Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT)

Stephanie A Hagstrom; Gui-Shuang Ying; Gayle J T Pauer; Gwen M Sturgill-Short; Jiayan Huang; David G Callanan; Ivana K Kim; Michael L Klein; Maureen G Maguire; Daniel F Martin; Comparison of AMD Treatments Trials Research Group

doi:10.1016/j.ophtha.2012.11.037

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Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT)

Journal article

Open access

Peer reviewed

Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT)

Stephanie A Hagstrom, Gui-Shuang Ying, Gayle J T Pauer, Gwen M Sturgill-Short, Jiayan Huang, David G Callanan, Ivana K Kim, Michael L Klein, Maureen G Maguire, Daniel F Martin, …

Ophthalmology (Rochester, Minn.), Vol.120(3), pp.593-599

03/2013

DOI: 10.1016/j.ophtha.2012.11.037

PMCID: PMC3633658

PMID: 23337555

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Abstract

To evaluate the pharmacogenetic relationship between genotypes of single nucleotide polymorphisms (SNPs) known to be associated with age-related macular degeneration (AMD) and response to treatment with ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech) for neovascular AMD. Clinical trial. Eight hundred thirty-four (73%) of 1149 patients participating in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 CATT clinical centers. Each patient was genotyped for SNPs rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3), using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA). Genotypic frequencies were compared with clinical measures of response to therapy at one year, including mean visual acuity (VA), mean change in VA, 15-letter or more increase in VA, retinal thickness, mean change in total foveal thickness, presence of fluid on OCT, presence of leakage on fluorescein angiography (FA), mean change in lesion size, and mean number of injections administered. 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. To adjust for multiple comparisons, P≤0.01 was considered statistically significant. No statistically significant differences in response by genotype were identified for any of the clinical measures studied. Specifically, there were no high-risk alleles that predicted final VA or change in VA, the degree of anatomic response (fluid on OCT or FA, retinal thickness, change in total foveal thickness, change in lesion size), or the number of injections. Furthermore, a stepwise analysis failed to show a significant epistatic interaction among the variants analyzed; that is, response did not vary by the number of risk alleles present. The lack of association was similar whether patients were treated with ranibizumab or bevacizumab or whether they received monthly or pro re nata dosing. Although specific alleles for CFH, ARMS2, HTRA1, and C3 may predict the development of AMD, they did not predict response to anti-vascular endothelial growth factor therapy.

Pharmacogenetics

Prospective Studies

Humans

Male

Vascular Endothelial Growth Factor A - antagonists & inhibitors

Macular Degeneration - diagnosis

Macular Degeneration - drug therapy

Bevacizumab

Ranibizumab

Serine Endopeptidases - genetics

Aged, 80 and over

Angiogenesis Inhibitors - therapeutic use

Female

Complement C3 - genetics

Visual Acuity - physiology

Fluorescein Angiography

Antibodies, Monoclonal, Humanized - therapeutic use

Tomography, Optical Coherence

Gene Frequency

High-Temperature Requirement A Serine Peptidase 1

Genotype

Proteins - genetics

Macular Degeneration - genetics

Aged

Polymorphism, Single Nucleotide

Complement Factor H - genetics

Details

Title: Subtitle: Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT)
Creators: Stephanie A Hagstrom - Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. Electronic address: hagstrs@ccf.org
Gui-Shuang Ying - Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
Gayle J T Pauer - Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
Gwen M Sturgill-Short - Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
Jiayan Huang - Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
David G Callanan - Texas Retina Associates, Arlington, Texas
Ivana K Kim - Harvard Medical School
Michael L Klein - Casey Eye Institute, Oregon Health Sciences Center, Portland, Oregon
Maureen G Maguire - Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
Daniel F Martin - Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
Comparison of AMD Treatments Trials Research Group
Contributors: James C Folk (Contributor) - University of Iowa, Ophthalmology and Visual Sciences
Douglas B Critser (Contributor) - University of Iowa, The University of Iowa Institute for Vision Research
Stephen R Russell (Contributor) - University of Iowa, Ophthalmology and Visual Sciences
Heather A Stockman (Contributor) - University of Iowa, Ophthalmology and Visual Sciences
Resource Type: Journal article
Publication Details: Ophthalmology (Rochester, Minn.), Vol.120(3), pp.593-599
DOI: 10.1016/j.ophtha.2012.11.037
PMID: 23337555
PMCID: PMC3633658
NLM abbreviation: Ophthalmology
ISSN: 0161-6420
eISSN: 1549-4713
Publisher: United States
Grant note: U10 EY017828 / NEI NIH HHS UL1 TR000439 / NCATS NIH HHS
Language: English
Date published: 03/2013
Academic Unit: The University of Iowa Institute for Vision Research; Ophthalmology and Visual Sciences
Record Identifier: 9983980064802771

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