Identifying RNA Biomarkers and Molecular Pathways Involved in Multiple Subtypes of Uveitis
| Autor: | Amr Zaki, Stephen R. Planck, Christopher D. Conrady, Suzanne S. Fei, Christina A. Harrington, Dongseok Choi, Albert T. Vitale, Robert P. Searles, Lynn M. Hassman, Lindsey Watson, Tammy M. Martin, Puthyda Keath, Sruthi Arepalli, James T. Rosenbaum, Claire Mitchell, Michael A. Paley |
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| Rok vydání: | 2021 |
| Předmět: |
Genetic Markers
Disease Inflammatory bowel disease Article Uveitis Transcriptome 03 medical and health sciences 0302 clinical medicine medicine Humans Gene Regulatory Networks RNA Messenger KEGG Eye Proteins Gene 030304 developmental biology 0303 health sciences business.industry Gene Expression Profiling medicine.disease Gene expression profiling Ophthalmology Gene Expression Regulation Immunology 030221 ophthalmology & optometry RNA Sarcoidosis business |
| Zdroj: | Am J Ophthalmol |
| ISSN: | 0002-9394 |
| DOI: | 10.1016/j.ajo.2021.01.007 |
| Popis: | Uveitis is a heterogeneous collection of diseases. We tested the hypothesis that despite the diversity of uveitides, there could be common mechanisms shared by multiple subtypes, and that evidence of these common mechanisms may be detected as gene expression profiles in whole blood.Cohort study.Ninety subjects with uveitis including axial spondyloarthritis (n = 17), sarcoidosis (n = 13), inflammatory bowel disease (n = 12), tubulointerstitial nephritis with uveitis (n = 10), or idiopathic uveitis (n = 38) as well as 18 healthy controls were enrolled, predominantly at Oregon HealthScience University. RNA-Seq data generated from peripheral, whole blood identified 19,859 unique transcripts. We analyzed gene expression pathways via Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO). We validated our list of upregulated genes by comparison to a previously published study on peripheral blood gene expression among 50 subjects with diverse forms of uveitis.Both the Kyoto Encyclopedia of Genes and Genomes and GO analysis identified multiple shared pathways or GO terms with a P value of.0001. Almost all pathways related to the immune response and/or response to an infection. A total of 119 individual transcripts were upregulated by at least 1.5-fold and false discovery rate.05, and 61 were downregulated by similar criteria. Comparing mRNA from our study with a false discovery rate.05 and the prior report, we identified 10 common gene transcripts: ICAM1, IL15RA, IL15, IRF1, IL10RB, GSK3A, TYK2, MEF2A, MEF2B, and MEF2D.Many forms of uveitis share overlapping mechanisms. These data support the concept that a single therapeutic approach could benefit diverse forms of this disease. |
| Databáze: | OpenAIRE |
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