Promoter Polymorphisms of TNF-α Gene as a Risk Factor for Schizophrenia

Suchanek-Raif, Renata; Raif, Paweł; Kowalczyk, Małgorzata; Paul-Samojedny, Monika; Kucia, Krzysztof; Merk, Wojciech; Kowalski, Jan

doi:10.1016/j.arcmed.2018.09.007

Cited by 15 publications

(9 citation statements)

References 33 publications

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“…Several studies have investigated the association of polymorphisms in the TNF-alpha gene and SCZ, but with inconsistent results [27,[30][31][32][33]. In the present study, both -308G>A and -1031C>T polymorphisms were not associated with SCZ, consistent with some of these studies [34][35][36], especially a study from China [37].…”

Section: Discussionsupporting

confidence: 77%

“…Moreover, we did not reveal a relationship between the 308G-1031C haplotype and SCZ. Inconsistent with our findings, a recent study in Poland found significant associations between the haplotype of TNF-alpha gene 1031T-863A-857C-308G, 1031C-863C-857C-308G, and 1031C-863C-857T-308G and increased risk of SCZ [33]. A possible mechanism for these inconsistent results is that the patients recruited in the study by Suchanek-Raife et al [33] were different than those in our study (paranoid subtype of SCZ vs SCZ).…”

Section: Discussionsupporting

confidence: 71%

“…Inconsistent with our findings, a recent study in Poland found significant associations between the haplotype of TNF-alpha gene 1031T-863A-857C-308G, 1031C-863C-857C-308G, and 1031C-863C-857T-308G and increased risk of SCZ [33]. A possible mechanism for these inconsistent results is that the patients recruited in the study by Suchanek-Raife et al [33] were different than those in our study (paranoid subtype of SCZ vs SCZ). Another explanation for the difference between TNF-alpha polymorphism and SCZ might be due to ethnic differences, as the frequency of -1301C>T and -308G>A genotypes varied significantly between different ethnicities.…”

Section: Discussionsupporting

confidence: 71%

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Association between TNF-alpha polymorphism and the age of first suicide attempt in chronic patients with schizophrenia

Lang

Trihn

et al. 2020

Aging

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Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 71%

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Association between TNF-alpha polymorphism and the age of first suicide attempt in chronic patients with schizophrenia

Lang

Trihn

et al. 2020

Aging

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“…TNF is a strong candidate gene for SZ. Serum levels of TNF were significantly increased in SZ, associated with more severe symptoms of SZ and with a higher risk of developing SZ (Suchanek-Raif et al, 2018 ). The mining of the existing FGFR1 ChiPseq data from our laboratory revealed that nFGFR1 direct binding to TNF receptor genes, as well as to the component genes of their receptor pathways, was increased in SZ ( Supplementary Figure S11 ).…”

Section: Discussionmentioning

confidence: 99%

Immune Factor, TNFα, Disrupts Human Brain Organoid Development Similar to Schizophrenia—Schizophrenia Increases Developmental Vulnerability to TNFα

Benson

Powell

Liput

et al. 2020

Front. Cell. Neurosci.

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Schizophrenia (SZ) is a neurodevelopmental genetic disorder in which maternal immune activation (MIA) and increased tumor necrosis factor-α (TNF-α) may contribute. Previous studies using iPSC-derived cerebral organoids and neuronal cells demonstrated developmental malformation and transcriptional dysregulations, including TNF receptors and their signaling genes, common to SZ patients with diverse genetic backgrounds. In the present study, we examined the significance of the common TNF receptor dysregulations by transiently exposing cerebral organoids from embryonic stem cells (ESC) and from representative control and SZ patient iPSCs to TNF. In control iPSC organoids, TNF produced malformations qualitatively similar in, but generally less pronounced than, the malformations of the SZ iPSC-derived organoids. TNF and SZ alone disrupted subcortical rosettes and dispersed proliferating Ki67 + neural progenitor cells (NPC) from the organoid ventricular zone (VZ) into the cortical zone (CZ). In the CZ, the absence of large ramified pan-Neu + neurons coincided with loss of myelinated neurites despite increased cortical accumulation of O4 + oligodendrocytes. The number of calretinin + interneurons increased; however, they lacked the preferential parallel orientation to the organoid surface. SZ and SZ+TNF affected fine cortical and subcortical organoid structure by replacing cells with extracellular matrix (ECM)-like fibers The SZ condition increased developmental vulnerability to TNF,

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“…It has been shown that patients with this disease suffer from disturbances in the expression of cytokines and chemokines with inter alia the affected levels of interleukin-1β (IL-1β), IL-2, IL-1 receptor antagonist (IL-1RA), and elevated production of IL-6, IL-8, tumour necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and C-C motif chemokine ligand 5 (CCL5 or RANTES) in blood or cerebrospinal fluid [43][44][45][46][47][48]. Additionally, polymorphisms in cytokine genes such as IL-2, IL-6, IL-10 and TNF-α are likely to be a risk factor for this disease [49][50][51]. Some postmortem studies have found the presence of activated microglia and changes in the levels of cytokines, chemokines and microglial markers [e.g., major histocompatibility complex class I (MHCI), MHCII, IL-1β, IL-6, IL-8] in brain tissues [39].…”

Section: Introductionmentioning

confidence: 99%

Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia

2021

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Schizophrenia has a complex and heterogeneous molecular and clinical picture. Over the years of research on this disease, many factors have been suggested to contribute to its pathogenesis. Recently, the inflammatory processes have gained particular interest in the context of schizophrenia due to the increasing evidence from epidemiological, clinical and experimental studies. Within the immunological component, special attention has been brought to chemokines and their receptors. Among them, CX3C chemokine receptor 1 (CX3CR1), which belongs to the family of seven-transmembrane G protein-coupled receptors, and its cognate ligand (CX3CL1) constitute a unique system in the central nervous system. In the view of regulation of the brain homeostasis through immune response, as well as control of microglia reactivity, the CX3CL1–CX3CR1 system may represent an attractive target for further research and schizophrenia treatment. In the review, we described the general characteristics of the CX3CL1–CX3CR1 axis and the involvement of this signaling pathway in the physiological processes whose disruptions are reported to participate in mechanisms underlying schizophrenia. Furthermore, based on the available clinical and experimental data, we presented a guide to understanding the implication of the CX3CL1–CX3CR1 dysfunctions in the course of schizophrenia.

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Promoter Polymorphisms of TNF-α Gene as a Risk Factor for Schizophrenia

Cited by 15 publications

References 33 publications

Association between TNF-alpha polymorphism and the age of first suicide attempt in chronic patients with schizophrenia

Association between TNF-alpha polymorphism and the age of first suicide attempt in chronic patients with schizophrenia

Immune Factor, TNFα, Disrupts Human Brain Organoid Development Similar to Schizophrenia—Schizophrenia Increases Developmental Vulnerability to TNFα

Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia

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