Association of TLR3 gene 1377C/T (rs3775290) and TLR7 gene C/G (rs3853839) polymorphism with hand, foot, and mouth disease caused by human enterovirus 71 infection susceptibility and severity in the Chinese Han population: A meta-analysis of case-control studies

Tian, Haokun; Xu, Weikai; Wen, Lequan; Tang, Lirui; Zhang, Mengjie; Song, Tiangang; Yang, Changsen

doi:10.1097/md.0000000000029758

Cited by 3 publications

(4 citation statements)

References 37 publications

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“…18 Moreover, TLR7 gene polymorphism is associated with susceptibility of human population to EV71. 19 However, the specific roles of TLR7 in the oral epithelial cells have not been fully revealed.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, oral epithelial cells including gingival keratinocytes are susceptible to HIV‐1 infection 16,17 . Also, TLR7 mediates cytokine responses to enterovirus 71 (EV71), an ssRNA virus which is one of the main causes of hand, foot, mouth disease (HFMD), in monocytic cells 18 and TLR7 gene polymorphism is associated with susceptibility of human population to EV71 19 . However, the role of TLR7 in GECs has not been fully revealed.…”

Section: Introductionmentioning

confidence: 99%

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TLR4/7‐mediated host‐defense responses of gingival epithelial cells

Chiba,

Tada,

Ohnishi

et al. 2024

J of Cellular Biochemistry

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Gingival epithelial cells (GECs) are physical and immunological barriers against outward pathogens while coping with a plethora of non‐pathogenic commensal bacteria. GECs express several members of Toll‐like receptors (TLRs) and control subsequent innate immune responses. TLR4 senses lipopolysaccharide (LPS) while TLR7/8 recognizes single‐strand RNA (ssRNA) playing important roles against viral infection. However, their distinct roles in GECs have not been fully demonstrated. Here, we analyzed biological responses of GECs to LPS and CL075, a TLR7/8 agonist. GE1, a mouse gingival epithelial cell line, constitutively express TLR4 and TLR7, but not TLR8, like primary skin keratinocytes. Stimulation of GE1 cells with CL075 induced cytokine, chemokine, and antimicrobial peptide expressions, the pattern of which is rather different from that with LPS: higher mRNA levels of interferon (IFN) β, CXCL10, and β‐defensin (BD) 14 (mouse homolog of human BD3); lower levels of tumor necrosis factor (TNF), CCL5, CCL11, CCL20, CXCL2, and CX3CL1. As for the intracellular signal transduction of GE1 cells, CL075 rapidly induced significant AKT phosphorylation but failed to activate IKKα/β‐NFκB pathway, whereas LPS induced marked IKKα/β‐NFκB activation without significant AKT phosphorylation. In contrast, both CL075 and LPS induced rapid IKKα/β‐NFκB activation and AKT phosphorylation in a macrophage cell line. Furthermore, specific inhibition of AKT activity abrogated CL075‐induced IFNβ, CXCL10, and BD14 mRNA expression in GE1 cells. Thus, TLR4/7 ligands appear to induce rather different host‐defense responses of GECs through distinct intracellular signaling mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TLR4/7‐mediated host‐defense responses of gingival epithelial cells

Chiba,

Tada,

Ohnishi

et al. 2024

J of Cellular Biochemistry

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“…Moreover, SARS-CoV-2 was associated with hepatitis in a male child carrying the rs179008-T allele, suggesting that hepatitis purportedly caused by SARS-CoV-2 infection could be associated with inefficient initial innate immune responses against the virus caused by the polymorphism [63]. Another TLR7 SNP (rs3853839G/C) had a relationship with Dengue virus infection [64], with HIV-1 infection and prognosis [65] and with Chikungunya virus infection in Indians [66], and was linked in Chinese patients to HCV persistence and predisposition to enterovirus-71-mediated hand, foot and mouth infection [67,68]. The function of rs3853839 and the expression of the TLR7 mRNA transcript in the development, severity and progression of COVID-19 was investigated in a study which suggested that the G/G genotype and the G allele could be a genetic risk factor for COVID-19 development, severe illness and poor clinical outcome in middle-aged individuals without comorbidities.…”

Section: Tlr7mentioning

confidence: 99%

TLRs: Innate Immune Sentries against SARS-CoV-2 Infection

Mantovani

Oliviero

Varchetta

et al. 2023

IJMS

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been responsible for a devastating pandemic since March 2020. Toll-like receptors (TLRs), crucial components in the initiation of innate immune responses to different pathogens, trigger the downstream production of pro-inflammatory cytokines, interferons, and other mediators. It has been demonstrated that they contribute to the dysregulated immune response observed in patients with severe COVID-19. TLR2, TLR3, TLR4 and TLR7 have been associated with COVID-19 severity. Here, we review the role of TLRs in the etiology and pathogenesis of COVID-19, including TLR7 and TLR3 rare variants, the L412F polymorphism in TLR3 that negatively regulates anti-SARS-CoV-2 immune responses, the TLR3-related cellular senescence, the interaction of TLR2 and TLR4 with SARS-CoV-2 proteins and implication of TLR2 in NET formation by SARS-CoV-2. The activation of TLRs contributes to viral clearance and disease resolution. However, TLRs may represent a double-edged sword which may elicit dysregulated immune signaling, leading to the production of proinflammatory mediators, resulting in severe disease. TLR-dependent excessive inflammation and TLR-dependent antiviral response may tip the balance towards the former or the latter, altering the equilibrium that drives the severity of disease.

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“…For example, the SNP of rs763110 in the gene that encodes FasL will lead to changes in FasL expression such that increased FasL expression and decreased Fas expression will help cancer cells escape tumor immune response, leading to gynecological and other types of cancers ( 8 ). Besides, the SNP of the TLR3 gene at rs5743305 are suggested to be linked to increased breast cancer risk, whereas the SNP of the TLR3 gene at rs3775291 are reportedly linked to breast cancer recurrence ( 9 ). Furthermore, the SNP of the cadherin gene at rs9929218 can cause colorectal cancer ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Association of CCL4 rs10491121 and rs1634507 gene polymorphisms with cancer susceptibility: trial sequential analysis and meta-analysis

Yang,

Song,

et al. 2023

Front. Oncol.

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BackgroundAlthough numerous case-control studies have explored the association between CC cytokine ligand-4 (CCL4) expression and cancer susceptibility, their results have been conflicting. This study aimed to determine the still-unknown connection of CCL4 rs10491121 and rs163450 polymorphisms with cancer susceptibility.MethodsSeveral databases, such as Web of Science, PubMed, and EMBASE, were searched for papers published since the creation of the database until November 2, 2022. Using RevMan 5.4 and StataMP 17 softwares, meta-analysis and subgroup analysis were performed after article screening and data extraction. For sensitivity analyses, one-by-one exclusion method was used, and then, the comprehensive effect was estimated and compared with that before exclusion. Trial sequential analysis (TSA)was performed using TSA 0.9.5.10 beta software.ResultsSeven case-control studies encompassing 3559 cases and 4231 controls were included. The P value was greater than 0.05 for all models, indicating the absence of an evident relationship of CCL4 gene rs10491121 and rs1634507 polymorphisms with cancer susceptibility. However, in the subgroup analysis of rs10491121, the P values in all models studied by us except GA vs. AA were <0.05 considering the Chinese subgroup, suggesting that the G allele is a risk factor for cancer in the Chinese population. Besides, in the subgroup analysis of rs1634507 considering oral cancer, the co-dominant model GG vs. TT, dominant model GG + GT vs. TT, and allele model G vs. T groups showed OR < 1 and P < 0.05, indicating that the G allele was a protective factor of oral cancer. However, for other cancer types, all the models studied by us except GG vs. GT showed OR > 1 and P < 0.05, indicating that the G allele was a risk factor for these other cancers. Despite the statistically significant results, sensitivity analysis had some stability limitations, and TSA results suggested the possibility of false positives.ConclusionFor rs10491121, we identified an association between the G allele and increased cancer risk in the Chinese population. For rs1634507, the G allele was not found to be associated with reduced risk of oral cancer and increased risk of other cancers studied by us.

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Association of TLR3 gene 1377C/T (rs3775290) and TLR7 gene C/G (rs3853839) polymorphism with hand, foot, and mouth disease caused by human enterovirus 71 infection susceptibility and severity in the Chinese Han population: A meta-analysis of case-control studies

Cited by 3 publications

References 37 publications

TLR4/7‐mediated host‐defense responses of gingival epithelial cells

TLR4/7‐mediated host‐defense responses of gingival epithelial cells

TLRs: Innate Immune Sentries against SARS-CoV-2 Infection

Association of CCL4 rs10491121 and rs1634507 gene polymorphisms with cancer susceptibility: trial sequential analysis and meta-analysis

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