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Polymorphic variability in the interleukin (IL)-1beta promoter conditions susceptibility to severe malarial anemia and functional changes in IL-1beta production.

Abstract
Interleukin (IL)-1beta is a cytokine released as part of the innate immune response to Plasmodium falciparum. Because the role played by IL-1beta polymorphic variability in conditioning the immunopathogenesis of severe malarial anemia (SMA) remains undefined, relationships between IL-1beta promoter variants (-31C/T and -511A/G), SMA (hemoglobin [Hb] level <6.0 g/dL), and circulating IL-1beta levels were investigated in children with parasitemia (n= 566) from western Kenya. The IL-1beta promoter haplotype -31C/-511A (CA) was associated with increased risk of SMA (Hb level <6.0 g/dL; odds ratio [OR], 1.98 [95% confidence interval {CI}, 1.55-2.27]; P < .05) and reduced circulating IL-1beta levels (p <.05). The TA (-31T/-511A) haplotype was nonsignificantly associated with protection against SMA (OR, 0.52 [95% CI, 0.18-1.16]; p =.11) and elevated IL-1beta production ( p<.05). Compared with the non-SMA group, children with SMA had significantly lower IL-1beta levels and nonsignificant elevations in both IL-1 receptor antagonist (IL-1Ra) and the ratio of IL-1Ra to IL-1beta. The results presented demonstrate that variation in IL-1beta promoter conditions susceptibility to SMA and functional changes in circulating IL-1beta levels.
AuthorsCollins Ouma, Gregory C Davenport, Gordon A Awandare, Christopher C Keller, Tom Were, Michael F Otieno, John M Vulule, Jeremy Martinson, John M Ong'echa, Robert E Ferrell, Douglas J Perkins
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 198 Issue 8 Pg. 1219-26 (Oct 15 2008) ISSN: 0022-1899 [Print] United States
PMID18781863 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Interleukin-1beta
Topics
  • Anemia (genetics, immunology, physiopathology)
  • Animals
  • Child, Preschool
  • Female
  • Genotype
  • Haplotypes
  • Humans
  • Infant
  • Interleukin-1beta (biosynthesis, blood, genetics)
  • Malaria, Falciparum (complications, genetics, immunology, parasitology)
  • Male
  • Parasitemia (complications, genetics, immunology, parasitology)
  • Plasmodium falciparum
  • Polymorphism, Genetic
  • Promoter Regions, Genetic (genetics)
  • Severity of Illness Index

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