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

G. Morahan*, C. S. Boutlis, D. Huang, A. Pain, J. R. Saunders, M. R. Hobbs, D. L. Granger, J. B. Weinberg, N. Peshu, E. D. Mwaikambo, K. Marsh, D. J. Roberts, N. M. Anstey

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

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 promoter 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.

Original languageEnglish (US)
Pages (from-to)414-418
Number of pages5
JournalGenes and Immunity
Volume3
Issue number7
DOIs
StatePublished - 2002

Keywords

  • Immune regulation
  • Interleukin-12
  • Severe malaria
  • Th1-Th2

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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