title: Interleukin-10 (IL-10) polymorphisms are associated with IL-10 production and clinical malaria in young children.
abstract: The role of interleukin-10 (IL-10) in malaria remains poorly characterized. The aims of this study were to investigate (i) whether genetic variants of the IL-10 gene influence IL-10 production and (ii) whether IL-10 production as well as the genotypes and haplotypes of the IL-10 gene in young children and their mothers are associated with the incidence of clinical malaria in young children. We genotyped three IL-10 single nucleotide polymorphisms in 240 children and their mothers from a longitudinal prospective cohort and assessed the IL-10 production by maternal peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs). Clinical episodes of Plasmodium falciparum malaria in the children were documented until the second year of life. The polymorphism IL-10 A-1082G (GCC haplotype of three SNPs in IL-10) in children was associated with IL-10 production levels by CBMC cultured with P. falciparum-infected erythrocytes (P = 0.043), with the G allele linked to low IL-10 production capacity. The G allele in children was also significantly associated with a decreased risk for clinical malaria infection in their second year of life (P = 0.016). Furthermore, IL-10 levels measured in maternal PBMCs cultured with infected erythrocytes were associated with increased risk of malaria infection in young children (P < 0.001). In conclusion, IL-10 polymorphisms and IL-10 production capacity were associated with clinical malaria infections in young children. High IL-10 production capacity inherited from parents may diminish immunological protection against P. falciparum infection, thereby being a risk for increased malaria morbidity.
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. guicheng.zhang@uwa.edu.au
authors.forename: Guicheng
authors.initials: G
authors.lastname: Zhang
authors.forename: Maria Nelia
authors.initials: MN
authors.lastname: Manaca
authors.forename: Michelle
authors.initials: M
authors.lastname: McNamara-Smith
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.forename: Augusto
authors.initials: A
authors.lastname: Nhabomba
authors.forename: Tamara Katherine
authors.initials: TK
authors.lastname: Berthoud
authors.forename: Siew-Kim
authors.initials: SK
authors.lastname: Khoo
authors.forename: Selma
authors.initials: S
authors.lastname: Wiertsema
authors.forename: Ruth
authors.initials: R
authors.lastname: Aguilar
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Barbosa
authors.forename: Llorenç
authors.initials: L
authors.lastname: Quintó
authors.forename: Pierre
authors.initials: P
authors.lastname: Candelaria
authors.forename: En Nee
authors.initials: EN
authors.lastname: Schultz
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Hayden
authors.forename: Jack
authors.initials: J
authors.lastname: Goldblatt
authors.forename: Caterina
authors.initials: C
authors.lastname: Guinovart
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
authors.forename: Peter N
authors.initials: PN
authors.lastname: Lesouëf
authors.forename: Carlota
authors.initials: C
authors.lastname: Dobaño
mesh_terms: D000328:Adult; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D007223:Infant; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011446:Prospective Studies
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10