Open Access Research article

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

John M Ong'echa12, Evans O Raballah13, Prakasha M Kempaiah2, Samuel B Anyona1, Tom Were1, Gregory C Davenport2, Stephen Konah1, John M Vulule4, Collins Ouma1, James B Hittner5 and Douglas J Perkins12*

Author Affiliations

1 University of New Mexico Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

2 Center for Global Health, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA

3 Department of Biochemistry and Biotechnology, Kenyatta University, Nairobi, Kenya

4 Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5 Department of Psychology, College of Charleston, Charleston, SC, USA

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BMC Genetics 2011, 12:69  doi:10.1186/1471-2156-12-69

Published: 6 August 2011

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<6.0g/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.