TLR4 gene polymorphisms rs11536889 is associated with intracranial aneurysm susceptibility

Liu, Liang; Zhang, Qin; Xiong, Xiao‐Yi; Gong, Qiuwen; Liao, Mao‐Fan; Yang, Qingwu

doi:10.1016/j.jocn.2018.04.074

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…As a member of the TLR family, TLR4 plays a crucial role in innate and adaptive immunity processes, which are involved in the pathogenesis of many inflammatory disorders (33). In previous studies, TLR4 was significantly associated with susceptibility to IA and expressed in IA walls (34)(35)(36). Furthermore, the TLR4 pathway promotes the development of IA rupture by accelerating inflammation in aneurysmal walls (34).…”

Section: Discussionmentioning

confidence: 99%

High-Dimensional Immune Profiling by Mass Cytometry Revealed the Circulating Immune Cell Landscape in Patients With Intracranial Aneurysm

Liu

Chan

et al. 2022

Front. Immunol.

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BackgroundIncreasing evidence supports a critical role of chronic inflammation in intracranial aneurysm (IA). Understanding how the immunological alterations in IA provides opportunities for targeted treatment. However, there is a lack of comprehensive and detailed characterization of the changes in circulating immune cells in IA.ObjectiveTo perform a comprehensive and detailed characterization of the changes in circulating immune cells in patients with IA.MethodsPeripheral blood mononuclear cell samples from IA patients (n = 26) and age-and sex-matched healthy controls (HCs, n = 20) were analyzed using high dimensional mass cytometry, and the frequency and phenotype of immune cell subtypes were assessed.ResultsWe identified 28 cell clusters and found that the immune signature of IA consists of cluster changes. IA patients exhibited dysfunction of immunity, with dysregulation of CD4+ T-cell clusters, increased B cells and monocytes, and decreased CD8+ T cells, DNT cells, and DPT cells. Moreover, compared with findings in HC, IA was associated with enhanced lymphocyte and monocyte immune activation, with a higher expression of HLA-DR, CXCR3, and CX3CR1. In addition, the expression of TLR4, p-STAT3, and the exhaustion marker PD1 was increased in T cells, B cells, and NK cells in IA patients.ConclusionsOur data provide an overview of the circulating immune cell landscape of IA patients, and reveal that the dysfunction of circulating immunity may play a potential role in the development of IA.

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Section: Discussionmentioning

confidence: 99%

High-Dimensional Immune Profiling by Mass Cytometry Revealed the Circulating Immune Cell Landscape in Patients With Intracranial Aneurysm

Liu

Chan

et al. 2022

Front. Immunol.

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“…TLR4 is expressed on endothelial cells, which may be an explanation for the involvement of vessel inflammation as a result of TLR4 activation. TLR4/MyD88 KO mice had a reduction in aneurysm rupture rates but not in incidence of aneurysm formation [ 85 , 86 , 87 ].…”

Section: Pathophysiology Of Inflammation After Sahmentioning

confidence: 99%

TLR4-Pathway-Associated Biomarkers in Subarachnoid Hemorrhage (SAH): Potential Targets for Future Anti-Inflammatory Therapies

Heinz

Schneider

2022

IJMS

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Subarachnoid hemorrhage is associated with severe neurological deficits for survivors. Among survivors of the initial bleeding, secondary brain injury leads to additional brain damage. Apart from cerebral vasospasm, secondary brain injury mainly results from cerebral inflammation taking place in the brain parenchyma after bleeding. The brain’s innate immune system is activated, which leads to disturbances in brain homeostasis, cleavage of inflammatory cytokines and, subsequently, neuronal cell death. The toll-like receptor (TLR)4 signaling pathway has been found to play an essential role in the pathophysiology of acute brain injuries such as subarachnoid hemorrhage (SAH). TLR4 is expressed on the cell surface of microglia, which are key players in the cellular immune responses of the brain. The participants in the signaling pathway, such as TLR4-pathway-like ligands, the receptor itself, and inflammatory cytokines, can act as biomarkers, serving as clues regarding the inflammatory status after SAH. Moreover, protein complexes such as the NLRP3 inflammasome or receptors such as TREM1 frame the TLR4 pathway and are indicative of inflammation. In this review, we focus on the activity of the TLR4 pathway and its contributors, which can act as biomarkers of neuroinflammation or even offer potential new treatment targets for secondary neuronal cell death after SAH.

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“…Toll-like receptor 4 (TLR4) is one of the receptors that closely related to immunity. [5] SNPs of genes encoding TLR4 often lead to a series of changes in the body’s immune system, leading to certain diseases, such as immune related diseases like asthma, [6] rheumatoid arthritis, [7] systemic lupus erythematosus, [8] and even intracranial aneurysm, [9] hypertension, [10] and endometriosis. [11]…”

Section: Introductionmentioning

confidence: 99%

“…Toll-like receptor 4 (TLR4) is one of the receptors that closely related to immunity. [5] SNPs of genes encoding TLR4 often lead to a series of changes in the body's immune system, leading to certain diseases, such as immune related diseases like asthma, [6] rheumatoid arthritis, [7] systemic lupus erythematosus, [8] and even intracranial aneurysm, [9] hypertension, [10] and endometriosis. [11] More and more case-control studies have confirmed that the SNPs of TLR4 gene 2026A/G (rs1927914), 896A/G (rs4986790), and 1196C/T (rs4986791) are related to the susceptibility and prognosis of prostate cancer, [12] lung cancer, [13] gastric cancer, [14] cervical cancer, [15] and many other cancers.…”

Section: Introductionmentioning

confidence: 99%

Association of TLR4 gene 2026A/G (rs1927914), 896A/G (rs4986790), and 1196C/T (rs4986791) polymorphisms and cancer susceptibility: Meta-analysis and trial sequential analysis

Wang

Wen

et al. 2023

Medicine

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Background: This study was performed to assess the association of TLR4 gene 2026A/G (rs1927914), 896A/G (rs4986790), and 1196C/T (rs4986791) polymorphisms and cancer susceptibility based on published case-control studies. Methods: Web of Science, PubMed, Embase, CBM, WanFang Data, CNKI, and VIP database were used for article retrieving. Then, these articles were screened according to the study inclusion and exclusion criteria. The data was extracted, and the study quality was evaluated according to the principle of Newcastle-Ottawa Scale. Meta-analysis was performed by RevMan 5.4 and Stata MP-17 software. Trial sequential analysis was performed by TSA 0.9.5.10 Beta software. Results: Eighty-seven case-control studies including 25,969 cases and 32,119 controls were included in the meta-analysis. The diseases involved in case groups include prostate cancer, lung cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, etc. A versus G model of rs1927914, A versus G model of rs4986790 and C versus T model of rs4986791 showed that odds ratio (OR) = 1.08, OR = 0.85, and OR = 0.74 respectively. All the 3 comparisons were statistically significant. Sensitivity analysis showed that the results were stable. Publication bias analysis and trial sequential analysis showed that no significant publication bias was found in the results of the meta-analysis, and the probability of false positives was small. Conclusion: People with A allele of rs1927914, G allele of rs4986790, or T allele of rs4986791 have higher risks of cancer. The results of meta-analysis are stable and have less probability of false positives.

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TLR4 gene polymorphisms rs11536889 is associated with intracranial aneurysm susceptibility

Cited by 8 publications

References 35 publications

High-Dimensional Immune Profiling by Mass Cytometry Revealed the Circulating Immune Cell Landscape in Patients With Intracranial Aneurysm

High-Dimensional Immune Profiling by Mass Cytometry Revealed the Circulating Immune Cell Landscape in Patients With Intracranial Aneurysm

TLR4-Pathway-Associated Biomarkers in Subarachnoid Hemorrhage (SAH): Potential Targets for Future Anti-Inflammatory Therapies

Association of TLR4 gene 2026A/G (rs1927914), 896A/G (rs4986790), and 1196C/T (rs4986791) polymorphisms and cancer susceptibility: Meta-analysis and trial sequential analysis

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