title: Genome-wide expression profiling of patients with primary open angle glaucoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Biostatistics Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Dilek
authors.initials: D
authors.lastname: Colak
authors.forename: Jose
authors.initials: J
authors.lastname: Morales
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bosley
authors.forename: Albandary
authors.initials: A
authors.lastname: Al-Bakheet
authors.forename: Banan
authors.initials: B
authors.lastname: AlYounes
authors.forename: Namik
authors.initials: N
authors.lastname: Kaya
authors.forename: Khaled K
authors.initials: KK
authors.lastname: Abu-Amero
mesh_terms: D000328:Adult; D000368:Aged; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D055106:Genome-Wide Association Study; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D012529:Saudi Arabia; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger