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Volume 6 Supplement 3

AIDS Vaccine 2009

P08-01. Heme oxygenase-1 promoter polymorphisms correlate with favorable virologic and immunological parameters in HIV-1 infection

Background

Since high levels of immune activation are predictive of progressive HIV disease, host immunoregulatory factors that blunt immune activation may contribute to delayed disease progression. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, is a potent anti-inflammatory protein that may represent one such factor.

Methods

We hypothesize that efficient up-regulation of HO-1 in response to HIV-1 infection is associated with more favorable clinical outcomes. To address this hypothesis, we conducted a candidate genotyping study of HO-1 promoter polymorphisms that are known to influence the magnitude and rapidity of HO-1 gene expression: a microsatellite (GT)n repeat and two single nucleotide polymorphisms (-1135 A/G) and (-413 A/T). Specific alleles of these genes have previously been shown to favor enhanced HO-1 gene expression and to correlate with favorable outcomes in non-HIV inflammatory diseases. Two patient groups were identified from the HIV-1 SCOPE cohort: elite controllers with no detectable viremia (n = 47) and non-controllers with viral loads > 10,000 (n = 218) in the absence of HAART.

Results

There was an enrichment of the HO-1 (-1135A) allele in Caucasian elite controllers compared to non-controllers (p < 0.009). We also observed that, among elite controllers, there was an association between the presence of the protective short (GT)=26 microsatellite repeat and lower levels of CD8+ T cell activation, as measured by surface staining of CD38 (p = 0.049). Haplotype analysis revealed a statistically significant enrichment of a specific haplotype [-1135(G), -413(A), GT>26] in the non-controller cohort (p = 0.04).

Conclusion

Our study demonstrates that Caucasian HIV-1 patients who maintain low levels of immune activation and control viral loads to undetectable levels are more likely to possess HO-1 promoter polymorphisms that favor enhanced HO-1 gene expression. These results suggest that efficient induction of HO-1 may play a role in limiting HIV-induced immune activation in the host, resulting in less immune dysfunction and better clinical outcomes.

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Correspondence to L Seu.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Seu, L., Burt, T., Williamson, D. et al. P08-01. Heme oxygenase-1 promoter polymorphisms correlate with favorable virologic and immunological parameters in HIV-1 infection. Retrovirology 6, P109 (2009). https://doi.org/10.1186/1742-4690-6-S3-P109

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Keywords

  • Viral Load
  • Immune Activation
  • Promoter Polymorphism
  • Microsatellite Repeat
  • Favorable Clinical Outcome