TY - JOUR
T1 - Increase in NF-κB binding affinity of the variant C allele of the toll-like receptor 9 -1237T/C polymorphism is associated with Helicobacter pylori-induced gastric disease
AU - Ng, Mike Tsz Hin
AU - Van't Hof, Rob
AU - Crockett, Julie C.
AU - Hope, Mairi E.
AU - Berry, Susan
AU - Thomson, John
AU - McLean, Mairi H.
AU - McColl, Kenneth E. L.
AU - El-Omar, Emad M.
AU - Hold, Georgina L.
PY - 2010/3/1
Y1 - 2010/3/1
N2 - 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-κB 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-κB. 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.
AB - 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-κB 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-κB. 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.
UR - http://www.scopus.com/inward/record.url?scp=77349109972&partnerID=8YFLogxK
U2 - 10.1128/IAI.01226-09
DO - 10.1128/IAI.01226-09
M3 - Article
C2 - 20038537
AN - SCOPUS:77349109972
SN - 0019-9567
VL - 78
SP - 1345
EP - 1352
JO - Infection and Immunity
JF - Infection and Immunity
IS - 3
ER -