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
| Autor: | James B. Hittner, Samuel B. Anyona, Stephen N. Konah, Prakasha Kempaiah, Gregory C. Davenport, John M. Vulule, Collins Ouma, Douglas J. Perkins, Tom Were, Evans Raballah, John M. Ong’echa |
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| Rok vydání: | 2011 |
| Předmět: |
Male
lcsh:QH426-470 Genotype Holoendemic 030231 tropical medicine Population Single-nucleotide polymorphism Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Immunity medicine Genetics Humans Genetics(clinical) Genetic Predisposition to Disease Longitudinal Studies Malaria Falciparum education Child 3' Untranslated Regions Genetics (clinical) 030304 developmental biology 0303 health sciences education.field_of_study biology Interleukin-12 Subunit p40 Infant Plasmodium falciparum Anemia SMA biology.organism_classification medicine.disease Kenya 3. Good health lcsh:Genetics Child Preschool Immunology Female Malaria Research Article |
| Zdroj: | BMC Genetics BMC Genetics, Vol 12, Iss 1, p 69 (2011) |
| ISSN: | 1471-2156 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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