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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A functional promoter variant in IL12B predisposes to cerebral malaria
Human Molecular Genetics, Volume 17, No. 14, Year 2008
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Description
The role of the Th1 pathway in the pathogenesis of severe malaria is unclear. We recently reported that a polymorphism with increasing IFNG transcription is associated with protection against cerebral malaria (CM). Interleukin-12 is required for Th1 cell differentiation, which is characterized by the production of interferon-γ. We investigated 21 markers in IL12 -related genes, including IL12A and IL12B encoding the two IL-12 (IL12p70) subunits, IL12p35 and IL12p40. We performed a family-based association study using a total sample set of 240 nuclear families. The IL12Bpro polymorphism was associated with susceptibility to CM. The CTCTAA allele and the GC/CTCTAA genotype are over-transmitted to children with CM (P = 0.0002 and 0.00002, respectively). We estimated the odds ratio to be 2.11 for risk of CM in heterozygous children [(95% confidence interval, 1.49-2.99); P < 0.0001]. Although the CTCTAA allele had a dominant effect on CM susceptibility, this effect is much stronger in heterozygous children, consistent with the functional effects of this allele in a heterozygous form. Heterozygosity for this polymorphism has been associated with reduced expression of the gene encoding IL12p40 and a low level of IL12p70 production. These results, together with the findings from immunological studies of low interferon-γ and IL-12 levels in CM, support a protective role for the Th1 pathway in CM. © The Author 2008. Published by Oxford University Press. All rights reserved.
Authors & Co-Authors
Marquet, Sandrine
France, Paris
Inserm
France, Marseille
Aix Marseille Université
Doumbo, Ogobara K.
Mali, Bamako
University of Bamako Faculty of Medicine, Pharmacy and Odonto-stomatology
Cabantous, Sandrine
France, Paris
Inserm
France, Marseille
Aix Marseille Université
Poudiougou, Belco
Mali, Bamako
University of Bamako Faculty of Medicine, Pharmacy and Odonto-stomatology
Argiro, Laurent
France, Paris
Inserm
France, Marseille
Aix Marseille Université
Safeukui, Innocent
France, Paris
Inserm
France, Marseille
Aix Marseille Université
Konaté, Salimata
Mali, Bamako
Gabriel Toure Hospital
Sissoko, Sibiri
Mali, Bamako
Gabriel Toure Hospital
Chevereau, Estelle
France, Paris
Inserm
France, Marseille
Aix Marseille Université
Traoré, Abdoulaye Mamadou
Mali, Bamako
University of Bamako Faculty of Medicine, Pharmacy and Odonto-stomatology
Kéita, Mamadou Marouf
Mali, Bamako
Gabriel Toure Hospital
Chevillard, Christophe
France, Paris
Inserm
France, Marseille
Aix Marseille Université
Abel, Laurent
France, Paris
L'institut Des Maladies Génétiques Imagine
Dessein, Alain Jacques J.
France, Paris
Inserm
France, Marseille
Aix Marseille Université
Statistics
Citations: 56
Authors: 14
Affiliations: 5
Identifiers
Doi:
10.1093/hmg/ddn118
ISSN:
09646906
e-ISSN:
14602083
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Case-Control Study