Association of Toll-Like Receptors 2, 4, 9 and 10 Genes Polymorphisms and Helicobacter pylori-Related Gastric Diseases in Saudi Patients

Eed, Emad M.; Hawash, Yousry; Khalifa, Amany Salah; Alsharif, Khalaf F.; Alghamdi, Saleh A.; Almalki, Abdulraheem Ali; Almehmadi, Mazen; Ismail, Khadiga Ahmed; Taha, Azza A.; Saber, Taisir

doi:10.4103/ijmm.ijmm_20_164

“…Nevertheless, our study found no correlation between TLR9 rs352140 genotypes and H. pylori -induced chronic gastritis, suggesting that this TLR might not influence the persistence of this infection in children. Another study that included patients with chronic gastritis, peptic ulcer disease, and gastric carcinoma showed that the TT genotype was more commonly expressed by patients from the chronic gastritis group[ 47 ]. Similarly, the meta-analysis of Zhang et al [ 48 ] pointed out a significant association between the TT variant genotype of TLR9 rs352140 SNP and the overall risk of neoplasia, emphasizing that this polymorphism might alter innate immune responses promoting chronic inflammation and subsequent carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Innate immunity – the hallmark of Helicobacter pylori infection in pediatric chronic gastritis

Meliţ

¹

,

Mărginean

²

,

Săsăran

³

et al. 2021

WJCC

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BACKGROUND Innate immunity was found to be associated with both persistence of Helicobacter pylori (H. pylori) infection and increased risk of gastric cancer. AIM To identify the risk factors associated with H. pylori infection and to establish the role of TLR9 rs352140 in suppressing or promoting inflammation related to this infection in children. METHODS We performed a study of 155 children with digestive symptoms, who were divided into two groups according to the histopathological exam: Group 1 – 48 children with H. pylori -induced chronic gastritis, and Group 2 – control group. RESULTS Rural area and poor living conditions were significantly associated with H. pylori chronic gastritis ( P = 0.0042/ P < 0.0001). Both positive immunoglobulin A anti H. pylori and the rapid urease test were significantly associated with H. pylori infection ( P < 0.0001). Significantly higher values of leukocytes and neutrophils within the peripheral blood were found in children with H. pylori chronic gastritis ( P = 0.111/ P = 0.284). We found a significant positive correlation between the variant TT genotype of TLR9 rs352140 polymorphism and both leucocytes and neutrophils ( P = 0.0225/ P = 0.0292). CONCLUSION Variant TT genotype carriers of the TLR9 rs352140 gene polymorphism might have a more severe degree of inflammation.

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“…Certain studies performed on patients with gastric cancer revealed a strong association between the previously mentioned SNPs of TLR2 and the risk for gastric carcinogenesis, as well as the prognosis of gastric cancer [30,31]. In contrast, other studies which assessed Japanese, Thai, and Saudi patients with H. pylori infection and H. pylori-associated gastropathies found no association between either of these two SNPs and the aforementioned conditions [32][33][34]. Similarly, we noticed no association between either TLR2 rs380499 or TLR2 rs384100 gene polymorphisms and the presence of chronic gastritis in children independently of the presence of H. pylori.…”

Section: Discussionmentioning

confidence: 99%

Innate Immune Responses in Pediatric Patients with Gastritis—A Trademark of Infection or Chronic Inflammation?

Meliţ

¹

,

Mărginean

²

,

Săsăran

³

et al. 2022

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The aim of this study was to define the relationship between several environmental, laboratory, and genetic factors, i.e., TLR2 and NLRP3 polymorphisms, and Helicobacter pylori (H. pylori) infection in children, by comparing three different groups of pediatric subjects: H. pylori-induced gastritis, non-H. pylori gastritis, and healthy controls. Our final study sample included 269 children, which were divided into three groups according to the histopathological exam: group 1 with 51 children with H. pylori-induced gastritis, group 2 with 103 children with H. pylori-negative gastritis, and group 3 (control group) with 115 children without any histopathological changes. All children underwent a thorough anamnesis, clinical exam, laboratory tests, and upper digestive endoscopy with gastric biopsy for rapid urease test, histopathological exam, and genetic analysis of TLR2 rs3804099, TLR2 rs3804100, and NLRP3 rs10754558 gene polymorphisms. We noticed a significant association between living conditions and the type of gastritis (p < 0.0001). Both rapid urease and serological tests were significantly associated with the presence of H. pylori (p < 0.0001). The CT variant genotype of TLR2 rs380499 was significantly associated with neutrophil count (p = 0.0325). We noticed a significant association between the CC variant genotype of NLRP3 rs10754558 and leucocytes, neutrophils, eosinophils, as well as ALT (p = 0.0185, p = 0.0379, p = 0.0483, p = 0.0356). Based on these findings, we state that poor living conditions and rural areas represent risk factors for H. pylori infection. The rapid urease test is a reliable diagnostic tool for this infection. CT and TT carriers of TLR2 rs3804099, as well as CC carriers of NLRP3 rs10754558, might display a more severe degree of systemic inflammation.

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“… 28 The rs4986790 GG geno-type may functionally reduce the TLR4 binding affinity to H pylori LPS, resulting in a weakened adaptive immune response compared to the wild TLR4 type, which may vary by population. 18 …”

Section: Discussionmentioning

confidence: 99%

“…The heterodimers formed from TLR10 that are expressed on the surface of gastric epithelial cells with TLR2 and/or TLR6 recognize multiple distinct patterns of H pylori LPS. 18 TLR10 (rs10004195) is linked with infection susceptibility, where the frequency of the TT genotype is reported to be 66% in H pylori- positive cases from a Chinese population. 29 Therefore, the T allele of TLR10 rs10004195 polymorphism showed an increased risk of chronic atrophic gastritis.…”

Section: Discussionmentioning

confidence: 99%

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Association of toll-like receptor 4, 5 and 10 polymorphisms with Helicobacter pylori -positive peptic ulcer disease in a center in Jordan

AL-Eitan

¹

,

Al-Momani

²

,

Al-Khatib

³

et al. 2021

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BACKGROUND: Helicobacter pylori infection is widespread, affecting about 50% of the global population. Polymorphisms in host genes such as the toll-like receptor 4 ( TLR4 ) might affect the susceptibility and severity of infection and treatment success. OBJECTIVE: Investigate the susceptibility and severity of H pylori infection with host TLR4 (rs11536889, rs4986790, rs200109652, rs10759932), TLR5 (rs5744174, rs2072493, rs746250566), TLR10 (rs559182335, rs10004195) polymorphisms. DESIGN: Analytical, cross-sectional. SETTING: Endoscopy clinic at tertiary care center. PATIENTS AND METHODS: Genomic DNA was extracted from formalin-fixed paraffin-embedded tissues collected from H pylori -infected patients and healthy individuals. The single nucleotide polymorphisms (SNPs) within the targeted TLR genes were genotyped to assess the genetic association of various SNPs with disease severity. MAIN OUTCOME MEASURES: Effect of genotype distribution on H pylori infection. SAMPLE SIZE: 250 peptic ulcer patients and 217 controls. RESULTS: The TLR10 genotype showed no significant association with H pylori infection except for rs10004195 (T>A) ( P =.002). The genotype frequency of Rs5744174 in TLR5 had a significant association with the presence of H pylori infection ( P =.046, OR=0.52). Except for gender (P=.022), there were no significant associations between clinical and demographic variables and SNPs relating to the severity of the H pylori infections. CONCLUSIONS: Our findings are consistent with differences in severity of H pylori infection due to TLR SNPs in different ethnic groups. Understanding differences in genetic susceptibility could help in classifying patients and matching patients with various treatment options on a genetic basis. LIMITATIONS: Lack of H pylori pathogenicity features assessment. CONFLICTS OF INTEREST: None.

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Association of Toll-Like Receptors 2, 4, 9 and 10 Genes Polymorphisms and Helicobacter pylori-Related Gastric Diseases in Saudi Patients

Cited by 17 publications

References 45 publications

Innate immunity – the hallmark of Helicobacter pylori infection in pediatric chronic gastritis

Innate immunity – the hallmark of Helicobacter pylori infection in pediatric chronic gastritis

Innate Immune Responses in Pediatric Patients with Gastritis—A Trademark of Infection or Chronic Inflammation?

Association of toll-like receptor 4, 5 and 10 polymorphisms with Helicobacter pylori -positive peptic ulcer disease in a center in Jordan

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