RGD Reference Report - Increase in NF-kappaB binding affinity of the variant C allele of the toll-like receptor 9 -1237T/C polymorphism is associated with Helicobacter pylori-induced gastric disease.

General

Increase in NF-kappaB binding affinity of the variant C allele of the toll-like receptor 9 -1237T/C polymorphism is associated with Helicobacter pylori-induced gastric disease.
Authors:	Ng, MT Van't Hof, R Crockett, JC Hope, ME Berry, S Thomson, J McLean, MH McColl, KE El-Omar, EM Hold, GL
Citation:	Ng MT, etal., Infect Immun. 2010 Mar;78(3):1345-52. Epub 2009 Dec 28.
RGD ID:	5130741
Pubmed:	PMID:20038537 (View Abstract at PubMed)
PMCID:	PMC2825916 (View Article at PubMed Central)
DOI:	DOI:10.1128/IAI.01226-09 (Journal Full-text)
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-kappaB 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-kappaB. 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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Achlorhydria		IAGP		5130741	DNA:SNP:promoter:g.-1237T>C (rs5743836) (human)	RGD
Achlorhydria		ISO	TLR9 (Homo sapiens)	5130741; 5130741	DNA:SNP:promoter:g.-1237T>C rs5743836 (human)	RGD

Objects Annotated

Genes (Rattus norvegicus)

Tlr9 (toll-like receptor 9)

Genes (Mus musculus)

Tlr9 (toll-like receptor 9)

Genes (Homo sapiens)

TLR9 (toll like receptor 9)

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Increase in NF-kappaB binding affinity of the variant C allele of the toll-like receptor 9 -1237T/C polymorphism is associated with Helicobacter pylori-induced gastric disease.