Increase in NF-kappa B Binding Affinity of the Variant C Allele of the Toll-Like Receptor 9-1237T/C Polymorphism Is Associated with Helicobacter pylori-Induced Gastric Disease

Ng, M. T. H., van't Hof, R., Crockett, J. C., Hope, M. E., Berry, S., Thomson, J., McLean, M. H., McColl, K. E. L., El Omar, E. M. and Hold, G. L. (2010) Increase in NF-kappa B Binding Affinity of the Variant C Allele of the Toll-Like Receptor 9-1237T/C Polymorphism Is Associated with Helicobacter pylori-Induced Gastric Disease. Infection and Immunity, 78(3), pp. 1345-1352.

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

• Item Type: Articles
• Keywords: allergy ASSOCIATION BACTERIAL-DNA BINDING CANCER CPG DNA CUTTING EDGE CYTOKINE GENE POLYMORPHISMS DENDRITIC CELLS DISEASE DISEASES EPITHELIAL-CELLS GASTRODUODENAL DISEASES GENE INCREASED RISK outcome OUTCOMES RISK RISK-FACTOR SINGLE-NUCLEOTIDE POLYMORPHISMS
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McColl, Professor Kenneth
• Authors: Ng, M. T. H., van't Hof, R., Crockett, J. C., Hope, M. E., Berry, S., Thomson, J., McLean, M. H., McColl, K. E. L., El Omar, E. M., and Hold, G. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences
• Journal Name: Infection and Immunity
• ISSN: 0019-9567