Toll-like receptor polymorphisms and cerebral malaria: TLR2 Delta 22 polymorphism is associated with protection from cerebral malaria in a case control study

作者：Greene Jennifer A; Sam Agudu Nadia; John Chandy C; Opoka Robert O; Zimmerman Peter A; Kazura James W^*

来源：Malaria Journal, 2012, 11: 47.

DOI：10.1186/1475-2875-11-47

• Malaria
• Toll-like receptor
• Plasmodium falciparum
• Polymorphism
• GPI

Background: In malaria endemic areas, host genetics influence whether a Plasmodium falciparum-infected child develops uncomplicated or severe malaria. TLR2 has been identified as a receptor for P. falciparum-derived glycosylphosphatidylinositol (GPI), and polymorphisms within the TLR2 gene may affect disease pathogenesis. There are two common polymorphisms in the 5%26apos; un-translated region (UTR) of TLR2, a 22 base pair deletion in the first unstranslated exon (Delta 22), and a GT dinucleotide repeat in the second intron (GTn). %26lt;br%26gt;Methods: These polymorphisms were examined in a Ugandan case control study on children with either cerebral malaria or uncomplicated malaria. Serum cytokine levels were analysed by ELISA, according to genotype and disease status. In vitro TLR2 expression was measured according to genotype. %26lt;br%26gt;Results: Both Delta 22 and GTn polymorphisms were highly frequent, but only Delta 22 heterozygosity was associated with protection from cerebral malaria (OR 0.34, 95% confidence intervals 0.16, 0.73). In vitro, heterozygosity for Delta 22 was associated with reduced pam3cys inducible TLR2 expression in human monocyte derived macrophages. In uncomplicated malaria patients, Delta 22 homozygosity was associated with elevated serum IL-6 (p = 0.04), and long GT repeat alleles were associated with elevated TNF (p = 0.007). %26lt;br%26gt;Conclusion: Reduced inducible TLR2 expression may lead to attenuated pro-inflammatory responses, a potential mechanism of protection from cerebral malaria present in individuals heterozygous for the TLR2 Delta 22 polymorphism.

• 出版日期2012-2-15