Polymorphic variability in the 3' untranslated region (UTR) of <it>IL12B </it>is associated with susceptibility to severe anaemia in Kenyan children with acute <it>Plasmodium falciparum </it>malaria

• Main Authors: Ong'echa John M, Raballah Evans O, Kempaiah Prakasha M, Anyona Samuel B, Were Tom, Davenport Gregory C, Konah Stephen, Vulule John M, Ouma Collins, Hittner James B, Perkins Douglas J
• Format: Article
• Language: English
• Published: BMC 2011-08-01
• Series: BMC Genetics
• Online Access: http://www.biomedcentral.com/1471-2156/12/69

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>malaria remains a leading cause of morbidity and mortality among African children. Innate immunity provides the first line of defence against <it>P. falciparum </it>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 <it>IL12B </it>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.</p> <p>Results</p> <p>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; <it>P </it>= 0.047, and AC: OR, 1.410; 95% CI, 0.953-2.087; <it>P </it>= 0.086) relative to wild type (AA). Although children with SMA had lower IL-12p40/p70 levels than the non-SMA group (<it>P </it>= 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.</p> <p>Conclusion</p> <p>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.</p>