Polymorphic variability in the interleukin (IL)-1beta promoter conditions susceptibility to severe malarial anemia and functional changes in IL-1beta production.
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.
Ouma
Collins
C
1University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
Davenport
Gregory C
GC
Awandare
Gordon A
GA
Keller
Christopher C
CC
Were
Tom
T
Otieno
Michael F
MF
Vulule
John M
JM
Martinson
Jeremy
J
Ong'echa
John M
JM
Ferrell
Robert E
RE
Perkins
Douglas J
DJ
D000740:Anemia / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D016778:Malaria, Falciparum / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D008297:Male; D018512:Parasitemia / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012720:Severity of Illness Index
D053583:Interleukin-1beta
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