Polymorphic Variability in the Interleukin (IL)-1Beta Promoter Conditions Susceptibility to Severe Malarial Anemia and Functional Changes in IL-1Beta Production
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Date
2008-10
Authors
Otieno, Micheal Frederick
Ouma, C.
Davenport, G. C.
Awandare, G. A.
Keller, C. C.
Were, T.
Vulule, J. M.
Martinson, J.
Ong'echa, J. M.
Ferrell, R. E.
Journal Title
Journal ISSN
Volume Title
Publisher
PubMed
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.
Description
doi: 10.1086/592055.