Polymorphisms in TLR9but not in TLR5increase the risk for duodenal ulcer and alter cytokine expression in the gastric mucosa

Colonization of the gastric mucosa by Helicobacter pylorican lead to peptic ulcer and gastric adenocarcinoma. TLRs are signaling receptors involved in the recognition of microorganisms, and polymorphisms in their genes may influence the innate and adaptive immune response to H. pylori, affecting the clinical outcomes of the infection. We assessed the association between single nucleotide polymorphisms in TLR9and TLR5and gastroduodenal diseases. All patients were genotyped by allelic discrimination in regions 1174C > T and 1775A > G of TLR5and −1237T > C and 2848G > A of TLR9. The 2848A allele of TLR9was more frequent in duodenal ulcer and showed an association of risk with this pathology. Polymorphisms in TLR5were not found to be associated with disease. Patients with polymorphisms in TLR9and TLR5expressed significantly lower levels of IL-1β and TNF-α, whereas polymorphisms in TLR5also decreased the expression of IL-6 and IL-10. Our findings suggest that 2848G > A polymorphism in TLR9increases the risk for the development of duodenal ulcer probably by modifying the inflammatory response to H. pyloriinfection. This is the first study to show an association of 2848A allele of TLR9with duodenal ulcer and with altered expression of inflammatory cytokines in the gastric mucosa.