Polymorphic Variability in the 3' Untranslated Region (UTR) of IL12B is associated with Susceptibility to Severe Anaemia in Kenyan Children with Acute Plasmodium falciparum Malaria

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dc.contributor.authorRaballah, E.
dc.contributor.authorOng'echa, J. M.
dc.contributor.authorKempaiah, P. M.
dc.contributor.authorAnyona, S. B.
dc.contributor.authorWere, T.
dc.contributor.authorDavenport, G. C.
dc.contributor.authorKonah, S.
dc.contributor.authorVulule, J. M.
dc.contributor.authorOuma, C.
dc.contributor.authorHittner, James B.
dc.contributor.authorPerkins, D. J.
dc.date.accessioned2014-02-03T11:40:41Z
dc.date.available2014-02-03T11:40:41Z
dc.date.issued2011-08
dc.descriptionDOI 10.1186/1471-2156-12-69en_US
dc.description.abstractBackground 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<6.0g/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.en_US
dc.identifier.citationBMC Genetics August 2011, 12:69,en_US
dc.identifier.issn1471-2156
dc.identifier.urihttp://ir-library.ku.ac.ke/handle/123456789/8908
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.titlePolymorphic Variability in the 3' Untranslated Region (UTR) of IL12B is associated with Susceptibility to Severe Anaemia in Kenyan Children with Acute Plasmodium falciparum Malariaen_US
dc.typeArticleen_US
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