Date Published:
12/2013

Publication Type:
Journal Article

Authors:

A.J. Levine
S. Horvath
E.N. Miller
E.J. Singer
P. Shapshak
G.C. Baldwin
O. Martínez-Maza
M.D. Witt
P. Langfelder

Secondary:
Journal of Neuroimmunology

Volume:
265

Pagination:
96-105

Issue:
1-2

URL:
https://pubmed.ncbi.nlm.nih.gov/

DOI:
10.1016/j.jneuroim.2013.09.016

Keywords:
External;Gene Expression;HIV-associated neurocognitive disorder;IL6R;Monocyte;transcriptome;WGCNA

Abstract:
<p>Immunologic dysfunction, mediated via monocyte activity, has been implicated in the development of HIV-associated neurocognitive disorder (HAND). We hypothesized that transcriptome changes in peripheral blood monocytes relate to neurocognitive functioning in HIV+ individuals, and that such alterations could be useful as biomarkers of worsening HAND.  METHODS: mRNA was isolated from the monocytes of 86 HIV+ adults and analyzed with the Illumina HT-12 v4 Expression BeadChip. Neurocognitive functioning, HAND diagnosis, and other clinical and virologic variables were determined. Data were analyzed using standard expression analysis and weighted gene co-expression network analysis (WGCNA).  RESULTS: Neurocognitive functioning was correlated with multiple gene transcripts in the standard expression analysis. WGCNA identified two nominally significant co-expression modules associated with neurocognitive functioning, which were enriched with genes involved in mitotic processes and translational elongation.  CONCLUSIONS: Multiple modified gene transcripts involved in inflammation, cytoprotection, and neurodegeneration were correlated with neurocognitive functioning. The associations were not strong enough to justify their use as biomarkers of HAND; however, the associations of two co-expression modules with neurocognitive functioning warrant further exploration.</p>