No reliable gene expression biomarkers of current or impending neurocognitive impairment in peripheral blood monocytes of persons living with HIV
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Events leading to and propagating neurocognitive impairment (NCI) in HIV-1-infected (HIV+) persons are largely mediated by peripheral blood monocytes. We previously identified expression levels of individual genes and gene networks in peripheral blood monocytes that correlated with neurocognitive functioning in HIV+ adults. Here, we expand upon those findings by examining if gene expression data at baseline is predictive of change in neurocognitive functioning 2 years later. We also attempt to validate the original findings in a new sample of HIV+ patients and determine if the findings are HIV specific by including HIV-uninfected (HIV−) participants as a comparison group. At two time points, messenger RNA (mRNA) was isolated from the monocytes of 123 HIV+ and 60 HIV− adults enrolled in the Multicenter AIDS Cohort Study and analyzed with the Illumina HT-12 v4 Expression BeadChip. All participants received baseline and follow-up neurocognitive testing 2 years after mRNA analysis. Data were analyzed using standard gene expression analysis and weighted gene co-expression network analysis with correction for multiple testing. Gene sets were analyzed for GO term enrichment. Only weak reproducibility of associations of single genes with neurocognitive functioning was observed, indicating that such measures are unreliable as biomarkers for HIV-related NCI; however, gene networks were generally preserved between time points and largely reproducible, suggesting that these may be more reliable. Several gene networks associated with variables related to HIV infection were found (e.g., MHC I antigen processing, TNF signaling, interferon gamma signaling, and antiviral defense); however, no significant associations were found for neurocognitive function. Furthermore, neither individual gene probes nor gene networks predicted later neurocognitive change. This study did not validate our previous findings and does not support the use of monocyte gene expression profiles as a biomarker for current or future HIV-associated neurocognitive impairment.
KeywordsHIV-associated neurocognitive disorders neuroHIV Monocyte WGCNA Gene expression Biomarker
We thank the participants and staff of the Multicenter AIDS Cohort Study in Los Angeles. This study was primarily funded by the National Institute for Drug Abuse [R01DA030913 (Levine and Horvath)]. The Los Angeles site of the Multicenter AIDS Cohort Study is funded by the National Institute of Allergy and Infectious Disease [U01-AI-35040 (Detels)], Los Angeles Biomedical Research Institute CTSI [UL1TR001881], and NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI [UL1TR000124].
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Conflict of interest
The authors declare that they have no conflict of interest.
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