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

BMC Genetics

Research Article

Prakasha M Kempaiah¹  Gregory C Davenport¹  John M Vulule²  James B Hittner³  Stephen Konah⁴  Collins Ouma⁴  Tom Were⁴  Samuel B Anyona⁴  Douglas J Perkins⁵  John M Ong'echa⁵  Evans O Raballah⁶ 

[1] Center for Global Health, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA;Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;Department of Psychology, College of Charleston, Charleston, SC, USA;University of New Mexico Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;University of New Mexico Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;Center for Global Health, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA;University of New Mexico Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;Department of Biochemistry and Biotechnology, Kenyatta University, Nairobi, Kenya;

关键词: Malaria;    Falciparum Malaria;    Severe Malaria;    Cerebral Malaria;    Rs3212227 Genotype;   

DOI  :  10.1186/1471-2156-12-69

 received in 2011-04-14, accepted in 2011-08-06,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundPlasmodium 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.ResultsMultivariate 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.ConclusionThe 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.

【 授权许可】

Unknown   
© Ong'echa et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.