Polymorphisms in TLR9 but not in TLR5 increase the risk for duodenal ulcer and alter cytokine expression in the gastric mucosa

Abstract

Colonization of the gastric mucosa by Helicobacter pylori can 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 TLR9 and TLR5 and gastroduodenal diseases. All patients were genotyped by allelic discrimination in regions 1174C>T and 1775A>G of TLR5 and -1237T>C and 2848G>A of TLR9. The 2848A allele of TLR9 was more frequent in duodenal ulcer and showed an association of risk with this pathology. Polymorphisms in TLR5 were not found to be associated with disease. Patients with polymorphisms in TLR9 and TLR5 expressed significantly lower levels of IL-1β and TNF-α, whereas polymorphisms in TLR5 also decreased the expression of IL-6 and IL-10. Our findings suggest that 2848G>A polymorphism in TLR9 increases the risk for the development of duodenal ulcer probably by modifying the inflammatory response to H. pylori infection. This is the first study to show an association of 2848A allele of TLR9 with duodenal ulcer and with altered expression of inflammatory cytokines in the gastric mucosa.

Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population

“…The authors of a previous study reported that the TLR9 gene causes an intracellular receptor signal cascade, and thus evokes nuclear transcription factors resulting in the production of pro-and anti-inflammatory cytokines (Hemmi et al, 2000). The authors of previous studies have reported that TLR9 gene polymorphisms are associated with the development of several inflammatory diseases (Bharti et al, 2014;Berenson et al, 2015;Trejo-de la O et al, 2015;Wen et al, 2015;Wujcicka et al, 2015). Bharti et al (2014) conducted a study in a Chinese population and assessed the association between TLR9 polymorphisms and pulmonary tuberculosis; they found that the TLR9 rs187084 polymorphism was associated with reduced risk of pulmonary tuberculosis.…”

“…Bharti et al (2014) conducted a study in a Chinese population and assessed the association between TLR9 polymorphisms and pulmonary tuberculosis; they found that the TLR9 rs187084 polymorphism was associated with reduced risk of pulmonary tuberculosis. Trejo-de la O et al (2015) conducted a study in a Mexican population and revealed that the A allele of TLR9+2848 was associated with increased risk of duodenal ulcers, and modified the expression of inflammatory cytokines in the gastric mucosa. Wen et al (2015) reported that TLR9+2848 had a correlation with systemic lupus erythematosus in a Chinese population.…”

Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high‐grade premalignant gastric lesions

“…We used samples from multiple studies to represent a wide range of Latin American populations from high‐ and low‐risk of GC, and of the whole spectrum of lesions from gastritis to GC. Details concerning eligibility, recruitment, data and sample collection, endoscopic examination and pathological diagnoses of each study have been published elsewhere 9,14‐20 . Subjects were at least 30 years old, and recruited from four countries in Latin America, with contrasting risk for GC, Venezuela (Tachira province) with high‐risk, Colombia with five cities representing both high‐ and low‐risk areas, and two countries with lower risk, Mexico (two hospitals in Mexico City) and Paraguay (two hospitals in Asunción City) in a varied period from the early 1990s to early 2000s; however, in each site recruitment time spanned no more than 3 years and all disease groups were collected within the same time period.…”

DNA Transfer and Toll-like Receptor Modulation by Helicobacter pylori

“…Similarly, TLR9 SNPs have been implicated in increasing gastric cancer risk (Hold et al 2009; Wang et al 2013; Trejo-de la et al 2015). Given the highly established relationship between H. pylori and gastric cancer, we and others have sought to determine the effects of H. pylori on TLR9-mediated responses and its possible implications in gastric carcinogenesis.…”