Characterization and strong risk association of TLR2 del -196 to -174 polymorphism and Helicobacter pylori and their influence on mRNA expression in gastric cancer

Lourenço, Caroline de Matos; Susi, Manoela Dias; Nascimento, Mariah Cristina Antunes do; Serafim, Vilson; Vila, Ana Paula Simedan; Rodrigues-Flemming, Gabriela Helena; Goloni-Bertollo, Eny Maria; Silva, Ana Elizabete; Oliveira-Cucolo, Juliana Garcia de

doi:10.4251/wjgo.v12.i5.535

Cited by 12 publications

(17 citation statements)

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“…Patients with a TT genotype of the TLR2 rs3804099 (19216T/C) polymorphism were found to be susceptible to CDI in our study. The TLR2 rs3804099 polymorphism has been connected to altered host immunity against bacterial infection (36)(37)(38). Of note, in recent years, the TLR2 rs3804099 polymorphism has been thoroughly investigated in association with Helicobacter pylori infection, another important pathogen in gastrointestinal disease (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

“…The TLR2 rs3804099 polymorphism has been connected to altered host immunity against bacterial infection (36)(37)(38). Of note, in recent years, the TLR2 rs3804099 polymorphism has been thoroughly investigated in association with Helicobacter pylori infection, another important pathogen in gastrointestinal disease (37)(38)(39). In studies in Iran and in Turkey, patients carrying the TLR2 rs3804099 CT genotype more frequently had peptic ulcers and H. pylori infection than healthy individuals (37,39).…”

Section: Discussionmentioning

confidence: 99%

“…In studies in Iran and in Turkey, patients carrying the TLR2 rs3804099 CT genotype more frequently had peptic ulcers and H. pylori infection than healthy individuals ( 37 , 39 ). Among individuals infected with H. pylori in Brazil, harboring the TLR2 rs3804099 (19216T/C) polymorphism had a protective effect in gastric carcinogenesis ( 38 ). The linkage of the TLR2 rs3804099 polymorphism to H. pylori infection suggests that this polymorphism has an important role in host immunity in the gastrointestinal system, which might explain the association between this polymorphism and CDI in our study.…”

Section: Discussionmentioning

confidence: 99%

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The Role of Toll-Like Receptor-2 in Clostridioides difficile Infection: Evidence From a Mouse Model and Clinical Patients

et al. 2021

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BackgroundClostridioides difficile is the leading cause of nosocomial infectious diarrhea. Toll-like receptors (TLRs) are the major components of innate immunity that sense pathogens. The relationship between TLRs and C. difficile infection (CDI) was analyzed in clinical patients and a mouse model.Materials and MethodsA prospective investigation was conducted in medical wards of Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan, from January 2011 to January 2013. Adult patients were followed up for the development of CDI. Single nucleotide polymorphisms (SNPs) of TLR2 and TLR4 were analyzed to assess the relationship between genetic polymorphisms and the development of CDI. A mouse model of CDI was used to investigate the pathogenic role of TLRs in CDI, TLR2 and TLR4 knockout (Tlr2-/- and Tlr4-/-) mice.ResultsIn the prospective study, 556 patients were enrolled, and 6.5% (36) of patients, accounting for 3.59 episodes per 1000 patient-days, developed CDI. Of 539 patients with available blood samples, the TLR2 rs3804099 polymorphism was more often noted in those with CDI than in those without CDI (64.5% vs. 46.1%; P = 0.046) but was not significant in multivariate analysis. Because the TLR2 rs3804099 polymorphism was moderately associated with CDI, the role of TLR2 and TLR4 was further evaluated in a mouse model. Both Tlr2-/- and Tlr4-/- mice showed more severe CDI disease than wild-type mice in terms of body weight change and fecal content five days after oral challenge with C. difficile. Furthermore, Tlr2-/- mice suffered from more severe disease than Tlr4-/- mice, as evidenced by stool consistency, cecum weight, and survival rate.ConclusionThe TLR2 rs3804099 polymorphism is marginally associated with the development of CDI, and the pathogenic role of TLR2 is further supported by a mouse model.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Role of Toll-Like Receptor-2 in Clostridioides difficile Infection: Evidence From a Mouse Model and Clinical Patients

et al. 2021

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“…The carriers of Del/Del genotype were found to have higher mRNA and protein expressions in colorectal cancer 38 . Besides this, in patients with gastric cancer, individuals with at least one −196 to −174 del allele had greater than 4‐fold higher mRNA expression of TLR2 gene than those with Ins/Ins or wild type genotype 39 . These findings suggest that Del/Del is a “high expressor” genotype.…”

Section: Discussionmentioning

confidence: 82%

“…38 Besides this, in patients with gastric cancer, individuals with at least one À196 to À174 del allele had greater than 4-fold higher mRNA expression of TLR2 gene than those with Ins/Ins or wild type genotype. 39 These findings suggest that Del/Del is a "high expressor" genotype. Higher prevalence of Del/Del genotype in GBS patients of this study suggests that this could lead to induction of immuneinflammatory responses by means of enhanced production of TLR2 molecules.…”

Section: Discussionmentioning

confidence: 98%

Variations within Toll‐like receptor (TLR) and TLR signaling pathway‐related genes and their synergistic effects on the risk of Guillain‐Barré syndrome

Dutta

Nagappa

Nair

et al. 2022

J Peripheral Nervous Sys

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Guillain‐Barré syndrome (GBS) is the commonest post‐infectious polyradiculopathy. Although genetic background of the host seems to play an important role in the susceptibility to GBS, genes conferring major risk are not yet known. Dysregulation of Toll‐like receptor (TLR) molecules exacerbates immune‐inflammatory responses and the genetic variations within TLR pathway‐related genes contribute to differential risk to infection. The aim of this study was to delineate the impact of genetic variations within TLR2, TLR3, and TLR4 genes as well as TLR signaling pathway‐related genes such as MyD88, TRIF, TRAF3, TRAF6, IRF3, NFκβ1, and IκBα on risk of developing GBS. Fourteen polymorphisms located within TLR2 (rs3804099, rs111200466), TLR3 (rs3775290, rs3775291), TLR4 (rs1927911, rs11536891), MyD88 (rs7744, rs4988453), TRIF (rs8120), TRAF3 (rs12147254), TRAF6 (rs4755453), IRF3 (rs2304204), NFκβ1 (rs28362491), and IκBα (rs696) genes were genotyped in 150 GBS patients and 150 healthy subjects either by PCR‐RFLP or TaqMan Allelic Discrimination Assay. Genotypes of two polymorphic variants, Del/Del of rs111200466 insertion and deletion (INDEL) polymorphism of TLR2 gene and TT of rs3775290 single nucleotide polymorphism (SNP) of TLR3 gene had significantly higher frequencies among GBS patients, while the frequencies of TT genotype of rs3804099 SNP of TLR2 gene and TT genotype of rs11536891 SNP of TLR4 gene were significantly higher in controls. Gene‐gene interaction study by Multifactor Dimensionality Reduction analysis also suggested a significant combined effect of TLR2, and NFκβ1 genes on the risk of GBS. The SNPs in the IκBα and IRF3 genes correlated with severity of GBS. The genes encoding TLRs and TLR signaling pathway‐related molecules could serve as crucial genetic markers of susceptibility and severity of GBS.

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Toll‐like receptors in health and disease

Wang,

Huang,

Zhan

et al. 2024

MedComm

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Toll‐like receptors (TLRs) are inflammatory triggers and belong to a family of pattern recognition receptors (PRRs) that are central to the regulation of host protective adaptive immune responses. Activation of TLRs in innate immune myeloid cells directs lymphocytes to produce the most appropriate effector responses to eliminate infection and maintain homeostasis of the body's internal environment. Inappropriate TLR stimulation can lead to the development of general autoimmune diseases as well as chronic and acute inflammation, and even cancer. Therefore, TLRs are expected to be targets for therapeutic treatment of inflammation‐related diseases, autoimmune diseases, microbial infections, and human cancers. This review summarizes the recent discoveries in the molecular and structural biology of TLRs. The role of different TLR signaling pathways in inflammatory diseases, autoimmune diseases such as diabetes, cardiovascular diseases, respiratory diseases, digestive diseases, and even cancers (oral, gastric, breast, colorectal) is highlighted and summarizes new drugs and related clinical treatments in clinical trials, providing an overview of the potential and prospects of TLRs for the treatment of TLR‐related diseases.

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Characterization and strong risk association of TLR2 del -196 to -174 polymorphism and Helicobacter pylori and their influence on mRNA expression in gastric cancer

Cited by 12 publications

References 40 publications

The Role of Toll-Like Receptor-2 in Clostridioides difficile Infection: Evidence From a Mouse Model and Clinical Patients

The Role of Toll-Like Receptor-2 in Clostridioides difficile Infection: Evidence From a Mouse Model and Clinical Patients

Variations within Toll‐like receptor (TLR) and TLR signaling pathway‐related genes and their synergistic effects on the risk of Guillain‐Barré syndrome

Toll‐like receptors in health and disease

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