Journal
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
Volume 82, Issue 4, Pages 548-555Publisher
AMER SOC TROP MED & HYGIENE
DOI: 10.4269/ajtmh.2010.09-0467
Keywords
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Funding
- National Institutes of Health Fogarty International Center [TW006794]
- National Institute of Neurological Disorders and Strokes [5R01NS055349-02]
- Fulbright African Regional Research Award
- National Institutes of Health [AI46919, TW007872]
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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.
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