TY - JOUR
T1 - 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
AU - Ong'echa, John M.
AU - Raballah, Evans O.
AU - Kempaiah, Prakasha M.
AU - Anyona, Samuel B.
AU - Were, Tom
AU - Davenport, Gregory C.
AU - Konah, Stephen
AU - Vulule, John M.
AU - Ouma, Collins
AU - Hittner, James B.
AU - Perkins, Douglas J.
N1 - Funding Information:
We are very grateful to the parents/guardians of the study participants and the children that participated in the study. We are also indebted to the Siaya District Hospital team and the University of New Mexico/KEMRI staff for support and management: Nicholas Kondiek and Martha Atandi for clinical support; Tabitha Otieno, Chris Wasonga, Joan Ochieng, and Godfrey Ogulla, for laboratory support; Vincent Omanje, Jared Ondijo and Caroline Odette for data management; Rodney Bosire for field support; and Anne Ong’ondo for administrative support. These data are published with the approval of the Director, Kenya Medical Research Institute (KEMRI). Financial support: This work was supported by grants from the National Institute of Health [R01 AI51305-04 and D43 TW05884-04 (DJP)] and Fogarty International Center [R01 TW007631 (JMO)]. The content is the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health. The funding body was not involved in the study design, collection, analysis, data interpretation, manuscript writing or the decision to submit the manuscript for publication.
PY - 2011/8/6
Y1 - 2011/8/6
N2 - 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.
AB - 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.
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U2 - 10.1186/1471-2156-12-69
DO - 10.1186/1471-2156-12-69
M3 - Article
C2 - 21819616
AN - SCOPUS:79961106971
SN - 1471-2156
VL - 12
JO - BMC genetics
JF - BMC genetics
M1 - 69
ER -