Differential contribution of interleukin-10 promoter variants in malaria and schistosomiasis mono- and co-infections among Nigerian children

ObjectiveInterleukin-10 (IL-10) is an anti-inflammatory cytokine produced by Th1 cells and macrophages. The rationale of this study was to examine and validate possible contributions of IL-10 promoter polymorphisms in sub-Saharan Africa in children infected with either Plasmodium falciparum or Schistosoma haematobium and in children co-infected with both parasites. Materials and MethodsA total of 309 Nigerian children aged 4-15 years were recruited. The study group consisted of individuals infected either with P. falciparum (n = 76) or S. haematobium (n = 94) in mono-infections, a group of children co-infected with both P. falciparum and S. haematobium (n = 62) and matched healthy controls (n = 77). The IL-10 promoter polymorphisms -1082G/A, -819C/T and -592C/A were genotyped by direct sequencing. ResultsThe frequencies of the IL-10 -1082GG genotype, the -1082G allele and haplotype GCC (positions -1082, -819 and -592) were higher in children infected with P. falciparum than in healthy controls, indicating that the -1082GG genotype and the -1082G allele and the GCC haplotype are associated with increased susceptibility to malaria infection (OR = 3.4, 95% CI = 1.2-10.8, P = 0.02; OR = 2.5, 95% CI = 1.1-3.4, P = 0.02; OR = 3.8, 95% CI = 2.0-7.2, P = 0.0001, respectively). Children with the -1082GG genotype had a higher parasitaemia than children with the -1082AA or -1082AG genotypes (P = 0.0017). Haplotype GCC occurred more frequently in children infected with S. haematobium, while haplotype GTA was less frequent than in controls (OR = 2.2, 95% CI = 1.2-4.4, P = 0.017 and OR = 0.1, 95% CI = 0.02-0.5, P = 0.0004, respectively). No differences in the frequencies of IL-10 promoter polymorphisms were observed between children with P. falciparum-S. haematobium co-infections and healthy controls. ConclusionAlthough IL-10 promoter polymorphisms are not associated with P. falciparum and S. haematobium co-infection, variant -1082G/A and haplotype GCC are associated with malaria, whereas the IL-10 haplotypes GCC and GTA are associated with schistosomiasis. ObjectifL'interleukine-10 (IL10) est une cytokine anti-inflammatoire produite par les cellules Th1 et les macrophages. Le rationnel de cette etude etait d'examiner et de valider les contributions possibles des polymorphismes du promoteur de IL10 en Afrique subsaharienne chez les enfants infectes par Plasmodium falciparum ou Schistosoma haematobium et chez ceux coinfectes par les deux parasites. Materiel et methodes309 enfants nigerians ages de 4 a 15 ans ont ete recrutes. Le groupe d'etude etait compose d'individus ayant des mono-infections par P. falciparum (n = 76) ou S. haematobium (n = 94), un groupe d'enfants coinfectes par P. falciparum et S. haematobium (n = 62) et des temoins sains apparies (n = 77). Les polymorphismes -1082G/A, -819C/T et -592C/A du promoteur de IL10 ont ete genotypes par sequencage direct. ResultatsLes frequences du genotype -1082GG de IL10, de l'allele -1082G et de l'haplotype GCC (positions -1082, -819 et -592) etaient plus elevees chez les enfants infectes par P. falciparum que chez les temoins sains, ce qui indique que le genotype -1082GG, l'allele -1082G et l'haplotype GCC sont associes a une susceptibilite accrue a l'infection paludique (OR = 3,4; IC95%: 1,2-10,8; p = 0,02, OR = 2,5; IC95%: 1,1-3,4; p = 0,02, OR = 3,8; IC95%: 2,0 a 7,2; p = 0,0001, respectivement). Les enfants avec le genotype -1082GG presentaient une parasitemie plus elevee que ceux avec les genotypes -1082AA ou -1082AG (p = 0,0017). L'haplotype GCC etait plus frequent chez les enfants infectes par S. haematobium, tandis que l'haplotype GTA etait moins frequent que chez les temoins (OR = 2,2; IC95%: 1,2-4,4; p = 0,017 et OR = 0,1; IC95%: 0,02-0,5; p = 0,0004, respectivement). Aucune difference dans les frequences des polymorphismes du promoteur de IL10 n'a ete observee entre les enfants atteints de coinfections a P. falciparum et S. haematobium et les controles sains. ConclusionBien que les polymorphismes du promoteur de IL10 ne soient pas associes a la coinfection a P. falciparum et S. haematobium, la variante -1082G/A et l'haplotype GCC sont associes au paludisme alors que les haplotypes GCC et GTA de IL10 sont associes a la schistosomiase.