title: Plasma microRNA profiling predicts HIV-associated neurocognitive disorder.
abstract: HIV-associated neurocognitive disorder (HAND) is a common neurological disorder among HIV-infected patients despite the availability of combination antiretroviral therapy. Host-encoded microRNAs (miRNA) regulate both host and viral gene expression contributing to HAND pathogenesis and can also serve as disease biomarkers. Herein, plasma miRNA profiles were investigated in HIV/AIDS patients with HAND.
  
  
  
  Discovery and Validation Cohorts comprising HIV/AIDS patients were studied that included patients with and without HAND (non-HAND). Plasma miRNA levels were measured by array hybridization and verified by quantitative real-time reverse transcriptase PCR (qRT-PCR). Multiple bioinformatic and biostatistical analyses were applied to the data from each cohort.
  
  
  
  Expression analyses identified nine miRNAs in the Discovery Cohort (HAND, n = 22; non-HAND, n = 25) with increased levels (≥two-fold) in the HAND group compared with the non-HAND group (P < 0.05). In the Validation Cohort (HAND, n = 12; non-HAND, n = 12) upregulation (≥two-fold) of three miRNAs (miR-3665, miR-4516 and miR-4707-5p) was observed in the HAND group that were also increased in the Discovery Cohort's HAND patients, which were verified subsequently by qRT-PCR. Receiver-operating characteristic curve analyses for the three miRNAs also pointed to the diagnosis of HAND (area under curve, 0.87, P < 0.005). Bioinformatics tools predicted that all three miRNAs targeted sequences of genes implicated in neural development, cell death, inflammation, cell signalling and cytokine functions.
  
  
  
  Differentially expressed plasma-derived miRNAs were detected in HIV/AIDS patients with HAND that were conserved across different patient cohorts and laboratory methods. Plasma-derived miRNAs might represent biomarkers for HAND and also provide insights into disease mechanisms.
authors.affiliation: aDepartment of Medicine (Neurology) bDepartment of Mathematical and Statistical Sciences cDepartment of Psychiatry, University of Alberta, Edmonton, Alberta dSouthern Alberta Clinic eDepartment of Medicine, University of Calgary, Calgary fDepartment of Medical Microbiology & Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Eugene L
authors.initials: EL
authors.lastname: Asahchop
authors.forename: Segun M
authors.initials: SM
authors.lastname: Akinwumi
authors.forename: William G
authors.initials: WG
authors.lastname: Branton
authors.forename: Esther
authors.initials: E
authors.lastname: Fujiwara
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
authors.forename: Christopher
authors.initials: C
authors.lastname: Power
mesh_terms: D015526:AIDS Dementia Complex / Q000175:diagnosis*; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D056808:Biostatistics; D015331:Cohort Studies; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D046228:Microarray Analysis; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010949:Plasma / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D035683:MicroRNAs