Abstract
Colonization of the gastric mucosa by Helicobacter pylori can lead to serious clinical outcomes, including gastric cancer. Toll-like receptors (TLRs) play an important role in the host response to H. pylori through the recognition of pathogen-associated molecular patterns. TLR9, in particular, is partly responsible for initiating bacterial induced immunity by binding unmethylated CpG-DNA, which is abundant in bacteria. A well-documented single nucleotide polymorphism (SNP) within the TLR9 promoter (TLR9 - 1237T/C), is associated with a variety of inflammatory disorders, including allergic asthma, inflammatory bowel disease, and atopy. Analysis of the TLR9 promoter gene sequence has shown that carriage of the variant "C" allele at position -1237 creates a potential NF-kappa B binding site that would theoretically increase the transcriptional activity of the gene. In this study, we report that the TLR9 -1237 C allele was significantly associated with the development of H. pylori-induced premalignant gastric changes. Functional analysis of the SNP, supporting the data generated from the genetic association study, showed that carriage of the C allele increased TLR9 transcriptional activity driven mainly by activation of NF-kappa B. Collectively, these findings confirm that the TLR9 -1237T/C polymorphism is a risk factor for the development of H. pylori-induced premalignant gastric changes and provide a plausible mechanistic explanation.
Original language | English |
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Pages (from-to) | 1345-1352 |
Number of pages | 8 |
Journal | Infection and Immunity |
Volume | 78 |
Issue number | 3 |
Early online date | 28 Dec 2009 |
DOIs | |
Publication status | Published - Mar 2010 |
Keywords
- single-nucleotide polymorphisms
- cytokine gene polymorphisms
- dendritic cells
- gastroduodenal diseases
- epithelial-cells
- increased risk
- bacterial-DNA
- cutting edge
- CPG DNA
- cancer