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Microarrays-Enabled Hypothesis Generation: The Suspect Role of FNBP-1 in Neuropsychiatric Pathogenesis Associated with HIV and/or HCVInfection

Abstract

Katsounas A, Wilting KR, Lempicki RA, Schlaak JF and Gerken G

Objective: The spectrum of neuropsychiatric illness (NI) associated with the Human Immunodeficiency Virus (HIV) and/or the Hepatitis C Virus (HCV) is far reaching and significantly impacts the clinical presentation and outcome of infected persons; however, the etiological and pathophysiological background remains partially understood. The present work was aimed to investigate the potential significance of formin binding protein 1 (FNBP-1)-dependent pathways in NI-pathogenesis by elaborating on previous microarray-based research in HIV and/or HCV-infected patients receiving interferon-? (IFN-?) immunotherapy via a rigorous data mining procedure. Methods: Using microarray data of peripheral whole blood (PB) samples obtained from HCV mono-infected persons (n=25, Affymetrix? HG-U133A_2) 12 h before and after the 1st dose of pegylated IFN-? (PegIFN-?), we reapplied the same analytical algorithm that we had developed and published in an earlier study with HIV/HCV coinfected subjects (N=28, Affymetrix? HG-U133A), in order to evaluate reproducibility of potential NI-related molecular findings in an independent cohort. Results: Among 28 gene expression profiles (HIV/HCV: N=9 vs. HCV: N=19) selected by applying different thresholds (a Mean Fold Difference value (MFD) in gene expression of ? 0.38 (log2) and/or P value from <0.05 to ? 0.1) FNBP-1 was identified as the only overlapping marker, which also exhibited a consistent upregulation in association with the development of NI in both cohorts. Previous functional annotation analysis had classified FNBP-1 as molecule with significant enrichment in various brain tissues (P<0.01). Conclusion: Our current findings are strongly arguing for intensifying research into the FNBP-1-related mechanisms that may be conferring risk for or resistance to HIV- and/or HCV-related NI.

மறுப்பு: இந்த சுருக்கமானது செயற்கை நுண்ணறிவு கருவிகளைப் பயன்படுத்தி மொழிபெயர்க்கப்பட்டது மற்றும் இன்னும் மதிப்பாய்வு செய்யப்படவில்லை அல்லது சரிபார்க்கப்படவில்லை

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