DNA methylation signatures of illicit drug injection and hepatitis C are associated with HIV frailty

Xinyu Zhang, Ying Hu, Amy C Justice, Boyang Li, Zuoheng Wang, Hongyu Zhao, John H Krystal and Ke Xu ()
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Xinyu Zhang: Yale School of Medicine
Ying Hu: National Cancer Institute Center for Biomedical Information & Information Technology
Amy C Justice: VA Connecticut Healthcare System
Boyang Li: Yale School of Public Health
Zuoheng Wang: Yale School of Public Health
Hongyu Zhao: Yale School of Public Health
John H Krystal: Yale School of Medicine
Ke Xu: Yale School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-02326-1

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