Microphotographs demonstrating TLR4 expression in gastric mucosa.

<p>The immunohistochemical staining of TLR4 expression in the body glands show expression mainly in the parietal cells (A), while in the glandular neck zone of the antrum (B) of stomach only occasional cells are positive. Double stainings (C, D) show TLR4 positivity (brown) in gastrin positive cells (red, C) and in somatostatin positive cells (red, D) in the antrum.</p

Dot diagram of gastrin-17 serum level distributions in the <i>TLR4</i> +896/+1196 genotypes with median value lines.

<p>P-values are calculated with Mann-Whitney U test.</p

<i>Toll-Like Receptor 4</i> Wild Type Homozygozity of Polymorphisms +896 and +1196 Is Associated with High Gastrin Serum Levels and Peptic Ulcer Risk

<div><p>Toll-like receptor 4 is a part of the innate immune system and recognizes <i>Helicobacter pylori</i> lipopolysaccharide. The goal of this study was to analyze the role of <i>Toll-like receptor 4</i> polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of <i>Helicobacter pylori</i> related gastroduodenal diseases in relation to gastric secretion and inflammation. <i>Toll-like receptor 4 polymorphisms</i>, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the <i>Toll-like receptor 4</i> +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of <i>Helicobacter pylori</i>. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). <i>Toll-like receptor 4</i> genotypes did not show any association with <i>Helicobacter pylori</i> positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the <i>Toll-like receptor 4</i> +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion.</p></div

Peptic ulcer risk.

<p>Active peptic ulcer risk in comparison with the non-ulcer dyspepsia patients in logistic regression models.</p><p>¹Versus +896/+1196 heterozygous and homozygous mutants</p><p>²Odds ratio</p><p>³95% confidence interval</p><p>⁴Stepwise forward (likelihood ratio criteria) model with <i>TLR4</i> polymorphisms, <i>cagA</i> positivity, smoking, age and sex as covariates.</p><p>Peptic ulcer risk.</p

<i>TLR4</i> genotypes and gastric histology.

<p>Variables are based on the Sydney system. Both non-ulcer dyspepsia and ulcer patients were included in analysis. Mean values are indicated.</p><p>¹Heterozygotes and homozygotes</p><p>²Mann-Whitney U test</p><p><i>TLR4</i> genotypes and gastric histology.</p