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Inflammation-related genes are associated with epigenetic aging in HIV

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Abstract

Chronic inflammation is characteristic of both HIV and aging (“inflammaging”) and may contribute to the accelerated aging observed in people living with HIV (PLWH). We examined whether three inflammation-related single-nucleotide polymorphisms (SNPs) were risk factors for accelerated aging and HIV-associated, non-AIDS (HANA) conditions among PLWH. We examined 155 postmortem cases with HIV (mean age = 47.3, 81% male, 68% self-reported White) from the National NeuroAIDS Tissue Consortium who had pre-mortem neurobehavioral/medical/virologic data and epigenomic data from occipital cortex tissue. Accelerated aging was measured according to the Epigenetic Clock; an aging biomarker based on DNA methylation levels. Past or current age-associated HANA conditions including cerebrovascular, liver and kidney disease, chronic obstructive pulmonary disease, cancer, and diabetes were determined via self-report. Epigenetic Aging Z-scores and likelihood of past/current HANA conditions were compared between major allele homozygotes and minor allele carriers for each SNP (IL-6 − 174G>C, IL-10 − 592C>A, TNF-α − 308 G>A) separately. Analyses were adjusted for relevant demographic/clinical factors. Epigenetic aging (e.g., higher Z-scores) was significantly greater in IL-6 C allele carriers (p = .002) and IL-10 CC homozygotes (p = .02) compared to other genotype groups. The likelihood of any past/current HANA condition did not differ by IL-10 genotype but was 3.36 times greater in IL-6 C allele carriers versus others (OR = 3.36, 95%CI = 1.09–10.34, p = .03). TNF-α genotype was not associated with epigenetic aging or HANA conditions. IL-6 and IL-10 SNPs may help to identify PLWH who are at high risk for accelerated aging. These insights into pathophysiological pathways may inform interventional approaches to treat rapid aging among PLWH.

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Acknowledgments

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the United States Government. The authors thank the staff of the NNTC, particularly Ben Gouaux for their help with this project.

Funding

Primary funding was from R01MH096648 (MPIs: Levine and Moore). Additional funding was provided from R01DA030913 (MPIs: Levine and Horvath) as well as the following National Institute of Health awards [P30MH062512, N01 MH22005, HHSN271201000036C and HHSN271201000030C, U24 MH100928, T32DA031098]. This work was further supported by salary support for Dr. E.E. Sundermann from the Interdisciplinary Research Fellowship in NeuroAIDS [R25MH081482] and support for Ms. M.A. Hussain from the Training in Research on Addictions in Interdisciplinary NeuroAIDS (TRAIN; T32DA031098).

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Authors and Affiliations

  1. Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA

    Erin E. Sundermann, Mariam A. Hussain & David J. Moore

  2. San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, 6363 Alvarado Ct, San Diego, CA, 92120, USA

    Mariam A. Hussain

  3. Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA

    Steven Horvath

  4. Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, USA

    Steven Horvath

  5. The Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada

    David T. S. Lin & Michael S. Kobor

  6. Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

    Andrew Levine

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  1. Erin E. Sundermann
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Correspondence to Erin E. Sundermann.

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Sundermann, E.E., Hussain, M.A., Moore, D.J. et al. Inflammation-related genes are associated with epigenetic aging in HIV. J. Neurovirol. 25, 853–865 (2019). https://doi.org/10.1007/s13365-019-00777-4

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