The Effect of TLR4 Asp299Gly polymorphism on IL-6 and IL -18 expression in H.pylori infected patients

Background & Aims: Helicobacter pylori (H. pylori) infection is associated with peptic ulcer and gastric cancer. Polymorphisms of the genes coding Toll-like receptors (TLRs) may influence the innate and adaptive immune responses and affect the susceptibility to H. pylori or the disease outcomes. But the details and association to different polymorphisms and different clinical expression in patients infected with H. pylori have remained unclear. The purpose of this study was to investigate the effect of TLR-4 Asp299Gly polymorphism on expression levels of IL-6 and IL-18 genes in patients infected with H. Pylori in comparison to uninfected patients. Methods: In a case-control study, biopsies were collected from 58 H. pylori-infected and 44 uninfected subjects.Genotypes of TLR-4 Asp299Gly single-nuleotide polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The expression levels of mucosal IL-6 and IL-18 mRNA were measured by real time-PCR. Cytokine expression levels in the two groups were analysed using the t test. Results: The frequencies of D/D and D/G genotypes were respectively 55.2% and 44.8% in H. pylori-infected and 77.2% and 22.8% in uninfected subjects. The expression level of IL-6 in H. pylori infected patients with TLR-4 gene polymorphism was significantly higher (P=0.001). However, no significant relationship between the expression level of IL-18 and TLR-4 gene polymorphism was reported in patients infected with H. pylori (P=0.419). In addition, no significant relationship between IL-6, IL-18 expression levels and TLR-4 gene polymorphism was reported in uninfected patients. Conclusion: TLR-4 Asp299Gly Gene single-nuclotide polymorphism increases the expression levels of TL-6 and has an important role in development of Hopylori-associated gastrititis.