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The influence of genetic variation on innate immune activation in an environment with high infectious pressure

Abstract

Interleukin-10 (IL-10) production is under tight genetic control in populations living in affluent environments. However, little is known about the role of IL10 genetics on cytokine production in populations living in environments with high infectious pressure. We have previously reported that, in a rural Ghanaian population, the most common IL10 haplotype associates with a pro-inflammatory response. Here, we aim to replicate these findings in an independent sample of the same population 2 years later. IL-10 and tumour necrosis factor-α (TNF-α) protein concentrations were determined in whole-blood samples ex vivo stimulated with lipopolysaccharide and zymosan in 2006 (n=615) and 2008 (n=647). The association between IL10 single nucleotide polymorphisms and Z-scores of IL-10 and TNF-α levels was analysed in each population subset. The most common IL10 haplotype was associated with a significantly lower IL-10 production and nonsignificantly increased TNF-α levels. The correlation between repeated cytokine assays, based on 111 individuals with measurements in both 2006 and 2008, was r=0.53 (P<0.001) for IL-10 and r=0.36 (P<0.001) for TNF-α. The replication of our previously found effect of variation in the IL10 gene on IL-10 production and the correlation between repeated cytokine stimulation assays provide evidence that IL10 genetics have an important role in regulating the host response under high infectious pressure.

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Acknowledgements

This research was supported by the Netherlands Foundation for the advancements of Tropical Research (WOTRO 93-467), the Netherlands Organisation for Scientific Research (grants NWO 051-14-050 and 050-60810), the EU funded Network of Excellence LifeSpan (EU FP6 036894), an unrestricted grant of the Board of the Leiden University Medical Center and the Association Dioraphte. None of these organisations had any role in the design, analysis, interpretation or report of the study.

We want to thank Margo van Schie-Troost and Marja Kersbergen-van Oostrom for their work on the cytokine assays.

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Correspondence to U K Eriksson.

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Boef, A., May, L., van Bodegom, D. et al. The influence of genetic variation on innate immune activation in an environment with high infectious pressure. Genes Immun 13, 103–108 (2012). https://doi.org/10.1038/gene.2011.57

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  • DOI: https://doi.org/10.1038/gene.2011.57

Keywords

  • interleukin-10
  • tumour necrosis factor-α
  • genetic variation
  • cytokines
  • innate immunity
  • Africa

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