Toll-like receptors are associated with helicobacter pylori infection and gastric mucosa pathology

Abstract

Background: Toll-like receptors (TLRs) mediate recognition of Helicobacter pylori and initiate the innate immune response to infection. Toll-like receptors polymorphisms are thought to influence susceptibility to H. pylori infection and H. pylori-related diseases. Objectives: To investigate the association of TLR polymorphisms with the susceptibility to H. pylori infection and various types of gastritis in Thai patients. Methods: The single nucleotide polymorphisms (SNPs) TLR1 rs4833095, TLR2 rs3804099 and rs3804100, TLR4 rs10759932 and TLR10 rs10004195 were analysed in 400 gastritis patients by real-time PCR using a TaqMan SNP Genotyping Assay. The association between TLR polymorphisms and the risk of H. pylori infection was investigated in 196 uninfected and 204 H. pylori-infected patients. The associations between TLR genotypes and the risk of gastric pathology changes, including chronic gastritis (N = 312 cases) and precancerous gastric lesions/gastric cancer (GC) (N = 88 cases), were examined. Univariate analysis was used to determine odds ratios (ORs) with confidence intervals (95% CIs). Results: Patients with the CC -or TT homozygous genotype for TLR1 rs4833095 had a significantly increased risk of H. pylori susceptibility (OR = 2.28, 95% CI = 1.27 - 7.60, P = 0.02 andOR= 1.34, 95% CI = 0.97-1.86, P = 0.04, respectively). Patients with the AA homozygous genotype for TLR10 rs10004195 had a significantly increased risk of H. pylori susceptibility (OR = 1.28, 95% CI = 0.98 - 1.76, P = 0.01) and exhibited a significantly increased risk of precancerous gastric lesions/GC (OR = 8.75, 95% CI = 2.78 - 14.24, P < 0.01). Conclusions: Our findings suggest that the TLR1 rs4833095 and TLR10 rs10004195 polymorphisms are potential genetic risk factors that modify the H. pylori infection susceptibility and influence the clinical manifestation of chronic gastritis, precancerous gastric lesions and GC in Thai patients.