Polymorphic variability in the IL-1β promoter conditions susceptibility to severe malarial anemia and functional changes in IL-1β production

• Published in: The Journal of infectious diseases Vol. 198; no. 8; pp. 1219 - 1226
• Main Authors: Ouma, Collins, Davenport, Gregory C., Awandare, Gordon A., Keller, Christopher C., Were, Tom, Otieno, Michael F., Vulule, John M., Martinson, Jeremy, Ong'echa, John M., Ferrell, Robert E., Perkins, Douglas J.
• Format: Journal Article
• Language: English
• Published: 15-10-2008
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/592055

Interleukin (IL)-1β is a cytokine released as part of innate immune response to
Plasmodium falciparum
. Since the role of IL-1β polymorphic variability in conditioning the immunopathogenesis of severe malarial anemia (SMA) remains undefined, relationships between IL-1β promoter variants (-31C/T and -511A/G), SMA (Hb<6.0 g/dL), and circulating IL-1β levels were investigated in parasitemic children (n=566) from western Kenya. IL-1β promoter haplotype -31C/-511A (CA) was associated with increased risk of SMA (Hb<6.0 g/dL; OR; 1.98, 95% CI, 1.55-2.27;
P
<0.05) and reduced circulating IL-1β levels (
P
<0.05). The TA (-31T/-511A) haplotype was non-significantly associated with protection against SMA (OR; 0.52, 95% CI, 0.18-1.16;
P
=0.11) and elevated IL-1β production (
P
<0.05). Children with SMA had significantly lower IL-1β levels and non-significant elevations in both IL-1 receptor antagonist (Ra) and the IL-1Ra:IL-1β ratio compared to the non-SMA group. Results presented demonstrate that variation in IL-1β promoter conditions susceptibility to SMA and functional changes in circulating IL-1β levels.