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

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-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.

• Authors: Nadia A Sam-Agudu, Jennifer A Greene, Robert O Opoka, James W Kazura, Michael J Boivin, Peter A Zimmerman, Melissa A Riedesel, Tracy L Bergemann, Lisa A Schimmenti, Chandy C John
• Journal: The American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 82 Issue 4 Pg. 548-55 (Apr 2010) ISSN: 1476-1645 [Electronic] United States
• PMID: 20348497 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• TLR2 protein, human
• TLR4 protein, human
• TLR9 protein, human
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Toll-Like Receptor 9
• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Child
• Child, Preschool
• Female
• Gene Expression Regulation (physiology)
• Genotype
• Humans
• Interferon-gamma (blood, genetics, metabolism)
• Malaria, Cerebral (metabolism)
• Male
• Polymorphism, Single Nucleotide
• Toll-Like Receptor 2 (genetics, metabolism)
• Toll-Like Receptor 4 (genetics, metabolism)
• Toll-Like Receptor 9 (genetics, metabolism)
• Tumor Necrosis Factor-alpha (blood, genetics, metabolism)