Polymorphic Variants of <i>TNFR2</i> Gene in Schizophrenia and Its Interaction with -308G/A <i>TNF-α</i> Gene Polymorphism

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

doi:10.1155/2018/8741249

Cited by 9 publications

(8 citation statements)

References 29 publications

(33 reference statements)

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“…Xiu et al ( 138 ) have suggested an important role for cytokine signaling in mediating the severity of cognitive dysfunction in schizophrenia and reported that the TNF-α 21031T/C polymorphism may not play a role in the predisposition of schizophrenia itself but may be implicated in the cognitive deficits of schizophrenia. In a case-control study, Suchanek-Raif et al ( 139 ) demonstrated that, for the TNFR2 gene, the genetic variants of rs3397, rs1061622, and rs1061624 are linked with a higher risk of developing schizophrenia and a more severe course in men. In contrast, the genotypes with a polymorphic allele for rs3397 SNP appear protective for women.…”

Section: Cytokine Polymorphisms In Schizophreniamentioning

confidence: 99%

Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment

2021

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Cytokines are one of the most important components of the immune system. They orchestrate the brain's response to infectious and other exogenous insults and are crucial mediators of the cross-talk between the nervous and immune systems. Epidemiological studies have demonstrated that severe infections and autoimmune disorders, in addition to genetic predisposition, are risk factors for schizophrenia. Furthermore, maternal infection during pregnancy appears to increase the risk of schizophrenia, and proinflammatory cytokines may be negatively involved in the neurodevelopmental process. A cytokine imbalance has been described in the blood and cerebrospinal fluid of schizophrenia patients, particularly in the T helper type 1 [Th1] and type 2 [Th2] cytokines, albeit the results of such studies appear to be contradictory. Chronic stress, likewise, appears to contribute to a lasting proinflammatory state and likely also promotes the disorder. The aim of this mini-review is to investigate the roles of different cytokines in the pathophysiology of schizophrenia and define how cytokines may represent key molecular targets to regulate for the prevention and treatment of schizophrenia. How current antipsychotic drugs impact cytokine networks is also evaluated. In this context, we propose to change the focus of schizophrenia from a traditionally defined brain disorder, to one that is substantially impacted by the periphery and immune system.

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Section: Cytokine Polymorphisms In Schizophreniamentioning

confidence: 99%

Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment

2021

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“…Polymorphisms of TGFB1, which encodes TGF-β, along with its additional overexpression [70] were also associated with schizophrenia [71]. Quite remarkably, polymorphisms of the TNFR2 gene encoding the TNF-α receptor, depending on the variant, may be associated with an increased risk of schizophrenia, or may have a protective effect [72].…”

Section: Immunogenetics Of Cytokine Alternations In Schizophreniamentioning

confidence: 99%

The Role of Cytokines in the Pathogenesis of Schizophrenia

Dawidowski

Górniak

Podwalski

et al. 2021

JCM

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Schizophrenia is a chronic mental illness of unknown etiology. A growing and compelling body of evidence implicates immunologic dysfunction as the key element in its pathomechanism. Cytokines, whose altered levels have been increasingly reported in various patient populations, are the major mediators involved in the coordination of the immune system. The available literature reports both elevated levels of proinflammatory as well as reduced levels of anti-inflammatory cytokines, and their effects on clinical status and neuroimaging changes. There is evidence of at least a partial genetic basis for the association between cytokine alterations and schizophrenia. Two other factors implicated in its development include early childhood trauma and disturbances in the gut microbiome. Moreover, its various subtypes, characterized by individual symptom severity and course, such as deficit schizophrenia, seem to differ in terms of changes in peripheral cytokine levels. While the use of a systematic review methodology could be difficult due to the breadth and diversity of the issues covered in this review, the applied narrative approach allows for a more holistic presentation. The aim of this narrative review was to present up-to-date evidence on cytokine dysregulation in schizophrenia, its effect on the psychopathological presentation, and links with antipsychotic medication. We also attempted to summarize its postulated underpinnings, including early childhood trauma and gut microbiome disturbances, and propose trait and state markers of schizophrenia.

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“…(2014) Variant was associated with autism risk whereby G allele seems to have a protective effect rs1061624 TNFR2 Neuroinflammatory response; neurogenesis AG (heterozygous) Stacey et al. (2017) A allele was associated with decreased hippocampal grey matter volume, compared to GG genotype Suchanek-Raif et al. (2018) GA genotype associated with higher risk of schizophrenia among individuals with a family history of SZ …”

Section: Resultsmentioning

confidence: 99%

“…The cells were found to be heterozygous for the second SNP on the TNFR2 gene, rs1061624. Even though this genotype has been associated with an increased risk of developing Schizophrenia ( Suchanek-Raif et al., 2018 ), this was only true for subjects with a family history of the disease and such information is not available for the donor of the HPC0A07/03C cell line.…”

Section: Variants With Demonstrated Associations With the Risk Of Neurological Or Psychiatric Diseasesmentioning

confidence: 99%

The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach

Lee

Metz

McDiarmid

et al. 2021

Brain, Behavior, & Immunity - Health

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Cell culture models are valuable tools to study biological mechanisms underlying health and disease in a controlled environment. Although their genotype influences their phenotype, subtle genetic variations in cell lines are rarely characterised and taken into account for in vitro studies. To investigate how the genetic makeup of a cell line might affect the cellular response to inflammation, we characterised the single nucleotide variants (SNPs) relevant to inflammation-related genes in an established hippocampal progenitor cell line (HPC0A07/03C) that is frequently used as an in vitro model for hippocampal neurogenesis (HN). SNPs were identified using a genotyping array, and genes associated with chronic inflammatory and neuroinflammatory response gene ontology terms were retrieved using the AmiGO application. SNPs associated with these genes were then extracted from the genotyping dataset, for which a literature search was conducted, yielding relevant research articles for a total of 17 SNPs. Of these variants, 10 were found to potentially affect hippocampal neurogenesis whereby a majority (n=7) is likely to reduce neurogenesis under inflammatory conditions. Taken together, the existing literature seems to suggest that all stages of hippocampal neurogenesis could be negatively affected due to the genetic makeup in HPC0A07/03C cells under inflammation. Additional experiments will be needed to validate these specific findings in a laboratory setting. However, this computational approach already confirms that in vitro studies in general should control for cell lines subtle genetic variations which could mask or exacerbate findings.

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Polymorphic Variants of TNFR2 Gene in Schizophrenia and Its Interaction with -308G/A TNF-α Gene Polymorphism

Cited by 9 publications

References 29 publications

Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment

Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment

The Role of Cytokines in the Pathogenesis of Schizophrenia

The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach

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