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A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production

Genes & Immunity volume 3, pages 414–418 (2002)Cite this article

Abstract

Interleukin-12 (IL-12) is an important regulatory cytokine in infection and immunity. Administration of IL-12 may reduce complications of severe malaria in rodents. Polymorphisms in IL12B, the gene encoding the IL-12 p40 subunit, influence the secretion of IL-12 and susceptibility to Type 1 diabetes. We therefore investigated whether IL12B polymorphisms may affect the outcome of severe malaria. Homozygosity for a polymorphism in the IL12B promoter was associated with increased mortality in Tanzanian children having cerebral malaria but not in Kenyan children with severe malaria. Furthermore, homozygotes for the IL12B promotor polymorphism had decreased production of nitric oxide, which is in part regulated by IL-12 activity. These studies suggest that IL12B polymorphisms, via regulation of IL-12 production, may influence the outcome of malaria infection in at least one African population.

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Acknowledgements

We thank Zhiqiang Wang for statistical advice, and Mushtaq Hassanali and Denis Manyenga for assistance with data collection. This paper is published with the approval of the Director of KEMRI.

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Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia

    G Morahan & D Huang

  2. Menzies School of Health Research, Darwin, NT, Australia

    C S Boutlis, J R Saunders & N M Anstey

  3. Nuffield Department of Clinical Laboratory Science, University of Oxford, UK

    A Pain & D J Roberts

  4. National Blood Service, UK

    A Pain & D J Roberts

  5. Division of Infectious Diseases, University of Utah, Salt Lake City, UT, USA

    M R Hobbs & D L Granger

  6. Departments of Medicine and Immunology, VA & Duke University Medical Centers, Durham, NC, USA

    J B Weinberg

  7. Kenya Medical Research Institute, Kilifi, Kenya

    N Peshu & K Marsh

  8. Muhimbili Medical Centre, Dar es Salaam, Tanzania

    E D Mwaikambo

Authors
  1. G Morahan
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  2. C S Boutlis
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  3. D Huang
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  4. A Pain
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  5. J R Saunders
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  6. M R Hobbs
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  7. D L Granger
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  8. J B Weinberg
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  9. N Peshu
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  10. E D Mwaikambo
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  11. K Marsh
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  12. D J Roberts
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  13. N M Anstey
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Corresponding author

Correspondence to G Morahan.

Additional information

This work was financially supported by the National Health and Medical Research Council of Australia and by a Special Program Grant from the NHMRC and the Juvenile Diabetes Research Foundation; National Institutes of Health RO1 AI41764, NHMRC Scholarship (CSB) and the Wellcome Trust, UK. DJR is a Howard Hughes International Research Scholar. No author has a commercial or other association that might pose a conflict of interest.

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Morahan, G., Boutlis, C., Huang, D. et al. A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production. Genes Immun 3, 414–418 (2002). https://doi.org/10.1038/sj.gene.6363909

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