TY - JOUR
T1 - Genome-wide expression profiling of patients with primary open angle glaucoma
AU - Colak, Dilek
AU - Morales, Jose
AU - Bosley, Thomas M.
AU - Al-Bakheet, Albandary
AU - AlYounes, Banan
AU - Kaya, Namik
AU - Abu-Amero, Khaled K.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/8
Y1 - 2012/8
N2 - Purpose. To identify differentially expressed genes and to elucidate gene interaction networks and molecular pathways possibly contributing to the development of POAG. Methods. Genome-wide expression profiling experiments were carried out using ABI high-density oligonucleotide microarrays in leukocytes from 25 POAG patients and 12 age-, ethnicity-, and sex-matched normal controls. Significantly modulated genes were defined as those with a false discovery rate (FDR) <0.01 and an absolute fold change (FC) >1.5. These genes are then mapped to relevant biologic processes and pathways. Results. We identified 563 genes that were significantly dysregulated (410 upregulated and 153 downregulated) in POAG compared with normal controls ("POAG gene signature"). These genes were significantly enriched with functions related to, among others, nucleoside, nucleotide, and nucleic acid metabolism, the mitogen-activated protein kinase kinase kinase cascade, apoptosis, protein synthesis, cell cycle, intracellular signaling cascade, and nervous system development and function. Among the most significantly altered canonical pathways in POAG were the ephrin receptor signaling, ubiquitin proteasome pathway, hypoxia signaling, neuregulin, and G-protein coupled receptor signaling. Network analysis revealed potentially critical roles of UBE2, TBP, GNAQ, SUMO1, CREB, p70S6k, IFNG, and CaMKII that are interacting with NF-κB, ubiquitin, proteasome, PI3K/AKT, IL12, and PDGF in the disease pathogenesis. Conclusions. Our study revealed blood gene signatures that clearly distinguish POAG patients and normal controls, as well as altered pathways that may shed light on POAG pathogenesis.
AB - Purpose. To identify differentially expressed genes and to elucidate gene interaction networks and molecular pathways possibly contributing to the development of POAG. Methods. Genome-wide expression profiling experiments were carried out using ABI high-density oligonucleotide microarrays in leukocytes from 25 POAG patients and 12 age-, ethnicity-, and sex-matched normal controls. Significantly modulated genes were defined as those with a false discovery rate (FDR) <0.01 and an absolute fold change (FC) >1.5. These genes are then mapped to relevant biologic processes and pathways. Results. We identified 563 genes that were significantly dysregulated (410 upregulated and 153 downregulated) in POAG compared with normal controls ("POAG gene signature"). These genes were significantly enriched with functions related to, among others, nucleoside, nucleotide, and nucleic acid metabolism, the mitogen-activated protein kinase kinase kinase cascade, apoptosis, protein synthesis, cell cycle, intracellular signaling cascade, and nervous system development and function. Among the most significantly altered canonical pathways in POAG were the ephrin receptor signaling, ubiquitin proteasome pathway, hypoxia signaling, neuregulin, and G-protein coupled receptor signaling. Network analysis revealed potentially critical roles of UBE2, TBP, GNAQ, SUMO1, CREB, p70S6k, IFNG, and CaMKII that are interacting with NF-κB, ubiquitin, proteasome, PI3K/AKT, IL12, and PDGF in the disease pathogenesis. Conclusions. Our study revealed blood gene signatures that clearly distinguish POAG patients and normal controls, as well as altered pathways that may shed light on POAG pathogenesis.
UR - http://www.scopus.com/inward/record.url?scp=84873031361&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873031361&partnerID=8YFLogxK
U2 - 10.1167/iovs.12-9634
DO - 10.1167/iovs.12-9634
M3 - Article
C2 - 22871836
AN - SCOPUS:84873031361
SN - 0146-0404
VL - 53
SP - 5899
EP - 5904
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 9
ER -