Evidence map›Paper›PMID 41279129›Full record

ArticlebioRxiv : the preprint server for biology2025

Identification and functional characterization of an AMD associated c-ABL binding SNP streak within the ARMS2 gene promoter region.

Ping-Wu Zhang, Sheng Liu, Weifeng Li, Laura Fan, Sean Li, Zi-He Wan, Cynthia A Berlinicke, Shannath L Merbs, Donald J Zack

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Ping-Wu ZhangDepartment of Ophthalmology, Stem Cell Ocular Regenerative Medicine Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine; Baltimore, MD, 21231, USA.
Sheng LiuDepartment of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Weifeng LiDepartment of Ophthalmology, Stem Cell Ocular Regenerative Medicine Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine; Baltimore, MD, 21231, USA.
Laura FanDepartment of Ophthalmology, Stem Cell Ocular Regenerative Medicine Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine; Baltimore, MD, 21231, USA.
Sean LiDepartment of Ophthalmology, Stem Cell Ocular Regenerative Medicine Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine; Baltimore, MD, 21231, USA.
Zi-He WanDepartment of Ophthalmology, Stem Cell Ocular Regenerative Medicine Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine; Baltimore, MD, 21231, USA.
Cynthia A BerlinickeDepartment of Ophthalmology, Stem Cell Ocular Regenerative Medicine Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine; Baltimore, MD, 21231, USA.
Shannath L MerbsDepartment of Ophthalmology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Donald J ZackDepartment of Ophthalmology, Stem Cell Ocular Regenerative Medicine Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine; Baltimore, MD, 21231, USA.

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI JEFFREY MUMM · 1985 to 2026
$22.1M
NEI NIH HHS P30 EY001765
6 · The paper itself

Abstract

Background: Large-scale genome-wide association studies (GWAS) have identified the human 10q26 locus as a major genetic risk factor for age-related macular degeneration (AMD). The AMD-associated interval has been refined to a 5,196 bp segment flanking the Methods: An unbiased bioinformatic screen identified a 5-SNP block within the 5,196 bp interval that potentially alters c-ABL protein binding. Protein-DNA interactions were validated using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Genetic association with AMD (dry and wet subtypes) was assessed in patient cohorts using blood genomic DNA. The regulatory effect of the 5-SNP block was further examined using luciferase reporter assays. Findings: We identified a 5-SNP block located ~556 bp upstream of the ARMS2 start codon, representing a cluster of predicted c-ABL tyrosine kinase binding sites. This block, in complete linkage disequilibrium with rs10490924 (A69S), showed a strong association with both wet and dry AMD (136 controls, 179 dry AMD, 251 wet AMD). EMSA and ChIP confirmed direct c-ABL binding, while luciferase reporter assays demonstrated reduced transcriptional activity mediated by the 5-SNP block in the presence of c-ABL. Interpretation: Our results suggest that the c-ABL-responsive 5-SNP regulatory streak in the ARMS2 promoter region act as functional non-coding elements that may contribute to AMD pathogenesis through altered transcriptional regulation.

Indexed as

Age-related macular degeneration (AMD)ARMS2c-ABLCis- and trans-acting elementgenetic associationProtein binding SNPsingle-nucleotide polymorphism (SNP)SNP streak

Identifiers

PMID41279129
PMCPMC12636363

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