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Nat Commun. 2017 Dec 21;8(1):2243. doi: 10.1038/s41467-017-02326-1.

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

Author information

1
Department of Psychiatry, Yale School of Medicine, 300 George Street, New Haven, CT, 06511, USA.
2
VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516, USA.
3
National Cancer Institute Center for Biomedical Information & Information Technology, 9609 Medical Center Drive, Bethesda, MD, 20850, USA.
4
Yale University School of Medicine, New Haven Veterans Affairs Connecticut Healthcare System, New Haven, CT, 06516, USA.
5
Department of Biostatistics, Yale School of Public Health, New Haven, CT, 06511, USA.
6
Department of Psychiatry, Yale School of Medicine, 300 George Street, New Haven, CT, 06511, USA. ke.xu@yale.edu.
7
VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516, USA. ke.xu@yale.edu.

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.

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