Abstract | BACKGROUND:
Plasmodium falciparum malaria remains a leading cause of morbidity and mortality among African children. Innate immunity provides the first line of defence against P. falciparum infections, particularly in young children that lack naturally-acquired malarial immunity, such as the population examined here. Consistent with the fact that elevated interleukin (IL)-12 is an important component of the innate immune response that provides protective immunity against malaria, we have previously shown that suppression of IL-12 in African children is associated with the development of severe malarial anaemia (SMA). Since the role of IL12B variants in conditioning susceptibility to SMA remains largely unexplored, the association between a single nucleotide polymorphism (1188A→C, rs3212227), SMA (Hb<6.0 g/dL), circulating IL-12p40/p70 levels, and longitudinal clinical outcomes in Kenyan children (n = 756) residing in a holoendemic falciparum malaria transmission area were investigated. RESULTS: Multivariate logistic regression analysis in children with acute malaria (n = 544) demonstrated that carriers of the C allele had increased susceptibility to SMA (CC: OR, 1.674; 95% CI, 1.006-2.673; P = 0.047, and AC: OR, 1.410; 95% CI, 0.953-2.087; P = 0.086) relative to wild type (AA). Although children with SMA had lower IL-12p40/p70 levels than the non-SMA group (P = 0.037), levels did not differ significantly according to genotype. Longitudinal analyses in the entire cohort (n = 756) failed to show any significant relationships between rs3212227 genotypes and either susceptibility to SMA or all-cause mortality throughout the three year follow-up. CONCLUSION: The rs3212227 is a marker of susceptibility to SMA in children with acute disease, but does not appear to mediate functional changes in IL-12 production or longitudinal outcomes during the acquisition of naturally-acquired malarial immunity.
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Authors | John M Ong'echa, Evans O Raballah, Prakasha M Kempaiah, Samuel B Anyona, Tom Were, Gregory C Davenport, Stephen Konah, John M Vulule, Collins Ouma, James B Hittner, Douglas J Perkins |
Journal | BMC genetics
(BMC Genet)
Vol. 12
Pg. 69
(Aug 06 2011)
ISSN: 1471-2156 [Electronic] England |
PMID | 21819616
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- 3' Untranslated Regions
- IL12B protein, human
- Interleukin-12 Subunit p40
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Topics |
- 3' Untranslated Regions
- Anemia
(complications, genetics, mortality)
- Child
- Child, Preschool
- Female
- Genetic Predisposition to Disease
- Genotype
- Humans
- Infant
- Interleukin-12 Subunit p40
(genetics)
- Kenya
- Longitudinal Studies
- Malaria, Falciparum
(complications, genetics)
- Male
- Polymorphism, Single Nucleotide
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