TLR9 polymorphisms are associated with altered IFN-gamma levels in children with cerebral malaria.

Nadia Sam-Agudu, Jennifer A. Greene, Robert Opoka, James W. Kazura, Michael J. Boivin, Peter A. Zimmerman, Melissa A. Riedesel, Tracy L. Bergemann, Lisa A. Schimmenti, Chandy C. John

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Abstract

Toll-like receptor (TLR) polymorphisms have been associated with disease severity in malaria infection, but mechanisms for this association have not been characterized. The TLR2, 4, and 9 single nucleotide polymorphism (SNP) frequencies and serum interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels were assessed in Ugandan children with cerebral malaria (CM, N = 65) and uncomplicated malaria (UM, N = 52). The TLR9 C allele at −1237 and G allele at 1174 were strongly linked, and among children with CM, those with the C allele at −1237 or the G allele at 1174 had higher levels of IFN-γ than those without these alleles (P = 0.03 and 0.008, respectively). The TLR9 SNPs were not associated with altered IFN-γ levels in children with UM or altered TNF-α levels in either group. We present the first human data that TLR SNPs are associated with altered cytokine production in parasitic infection.

Original languageUndefined/Unknown
JournalPaediatrics and Child Health, East Africa
DOIs
Publication statusPublished - 1 Apr 2010

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