TLR9 Polymorphisms Are Associated with Altered IFN-γ Levels in Children with Cerebral Malaria

• Published in: The American journal of tropical medicine and hygiene 2010-04, Vol.82 (4), p.548-555
• Main Authors: SAM-AGUDU, Nadia A, GREENE, Jennifer A, OPOKA, Robert O, KAZURA, James W, BOIVIN, Michael J, ZIMMERMAN, Peter A, RIEDESEL, Melissa A, BERGEMANN, Tracy L, SCHIMMENTI, Lisa A, JOHN, Chandy C
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Child; Child, Preschool; Female; Gene Expression Regulation - physiology; Genotype; Human protozoal diseases; Humans; Infectious diseases; Interferon-gamma - blood; Interferon-gamma - genetics; Interferon-gamma - metabolism; Malaria; Malaria, Cerebral - metabolism; Male; Medical sciences; Parasitic diseases; Polymorphism, Single Nucleotide; Protozoal diseases; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-Like Receptor 9 - genetics; Toll-Like Receptor 9 - metabolism; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.2010.09-0467

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-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) 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-gamma than those without these alleles (P = 0.03 and 0.008, respectively). The TLR9 SNPs were not associated with altered IFN-gamma levels in children with UM or altered TNF-alpha levels in either group. We present the first human data that TLR SNPs are associated with altered cytokine production in parasitic infection.