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Variations in the heme oxygenase-1 microsatellite polymorphism are associated with plasma CD14 and viral load in HIV-infected African-Americans

Genes & Immunity volume 13, pages 258–267 (2012)Cite this article

Abstract

Heme oxygenase-1 (HO-1) is an anti-inflammatory enzyme that maintains homeostasis during cellular stress. Given previous findings that shorter length variants of a HO-1 promoter region GTn microsatellite polymorphism are associated with increased HO-1 expression in cell lines, we hypothesized that shorter variants would also be associated with increased levels of HO-1 expression, less inflammation and lower levels of inflammation-associated viral replication in human immunodeficiency virus (HIV)-infected subjects. Healthy donors (n=20) with shorter GTn repeats had higher HO-1 mRNA transcript in peripheral blood mononuclear cells stimulated with lipopolysaccharide (r=−0.38, P=0.05). The presence of fewer GTn repeats in subjects with untreated HIV disease was associated with higher HO-1 mRNA levels in peripheral blood (r=−0.41, P=0.02); similar observations were made in CD14+ monocytes from antiretroviral-treated subjects (r=−0.36, P=0.04). In African-Americans, but not Caucasians, greater GTn repeats were correlated with higher soluble CD14 levels during highly active antiretroviral therapy (r=0.38, P=0.007) as well as higher mean viral load off-therapy (r=0.24, P=0.04). These data demonstrate that the HO-1 GTn microsatellite polymorphism is associated with higher levels of HO-1 expression and that this pathway may have important effects on the association between inflammation and HIV replication.

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Acknowledgements

We would like to thank all participants from the San Francisco General Hospital and San Francisco Veteran Affairs Medical centers. We would like to thank Dr David Williamson for his help in setting up the HO-1 SNP assay as well as curation of DNA samples. L.S. was supported by a pre-doctoral dissertation California HIV Research Program Grant (#D09-SF-313). During the period in which this work was carried out, T.D.B. was a fellow of the Pediatric Scientist Development Program and was supported by the American Pediatric Society, the American Academy of Pediatrics and the March of Dimes. J.M.M. was supported by NIH Awards U01 AI43641 and R37 AI40312, and is the recipient of the National Institutes of Health Director's Pioneer Award, part of the National Institutes of Health Roadmap for Medical Research, through Grant DPI OD00329. The SCOPE cohort was supported by the Centers for AIDS Research at UCSF (PO AI27763), CFAR Network of Integrated Systems (R24 AI067039), the UCSF CTSI (UL1 RR024131), NIAID (RO1 AI087145, K24AI069994, AI-76174, amfAR and the Ragon Institute. We would also like to thank Christopher R. Gignoux for critical discussion during the preparation of the manuscript.

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Authors and Affiliations

  1. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA

    L Seu

  2. Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA, USA

    L Seu, T D Burt & J M McCune

  3. Division of Neonatology, Department of Pediatrics, University of California, San Francisco, CA, USA

    T D Burt

  4. Institute for Human Genetics, University of California, San Francisco, CA, USA

    J S Witte

  5. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    J S Witte & J N Martin

  6. Department of Medicine, Positive Health Program, University of California, San Francisco, CA, USA

    S G Deeks

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  1. L Seu
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Correspondence to J M McCune.

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Seu, L., Burt, T., Witte, J. et al. Variations in the heme oxygenase-1 microsatellite polymorphism are associated with plasma CD14 and viral load in HIV-infected African-Americans. Genes Immun 13, 258–267 (2012). https://doi.org/10.1038/gene.2011.76

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