Abstract
Intravenous illicit drug use (IDU) and hepatitis C infection (HCV) commonly co-occur among HIV-infected individuals. These co-occurring conditions may produce interacting epigenetic effects in white blood cells that influence immune function and health outcomes. Here, we report an epigenome-wide association analysis comparing IDU+/ HCV+ and IDU−/HCV− in 386 HIV-infected individuals as a discovery sample and in 412 individuals as a replication sample. We observe 6 significant CpGs in the promoters of 4 genes, NLRC5, TRIM69, CX3CR1, and BCL9, in the discovery sample and in meta-analysis. We identify 19 differentially methylated regions on chromosome 6 harboring MHC gene clusters. Importantly, a panel of IDU+/HCV+-associated CpGs discriminated HIV frailty based upon a validated index with an area under the curve of 79.3% for high frailty and 82.3% for low frailty. These findings suggest that IDU and HCV involve epigenetic programming and that their associated methylation signatures discriminate HIV pathophysiologic frailty.
Highlights
Intravenous illicit drug use (IDU) and hepatitis C infection (HCV) commonly co-occur among HIV-infected individuals
Consistent with the signals from DNA-me positions (DMPs), we found a DMR in the promoter of TRIM69 containing 5 CpG sites associated with IDU+/HCV+
Consistent with our hypothesis, the results of DMP, DMR, gene pathway, and network analyses suggest that IDU+/HCV+ involves epigenetic programming of immune- and inflammationrelated genes
Summary
Intravenous illicit drug use (IDU) and hepatitis C infection (HCV) commonly co-occur among HIV-infected individuals These co-occurring conditions may produce interacting epigenetic effects in white blood cells that influence immune function and health outcomes. We recently reported that the methylation of genes in immune and inflammation domains in white blood cells (WBC) differed significantly between HIV-infected and uninfected individuals[19]. These findings and others suggest that disease outcomes might be worsened by epigenetic effects of comorbid addictions and, by implication, improved by treatments that target epigenetic processes[20, 21]. We first profile epigenome-wide DNA-me in 386 HIV-infected IDU+/HCV+ individuals and in IDU−/HCV
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
