The functional significance of the TGM2 gene in schizophrenia: A correlation of SNPs and circulating IL-2 levels

Bradford, Matilda; Law, Matthew H.; Megson, Ian L.; Wei, Jun

doi:10.1016/j.jneuroim.2010.09.007

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…Reduced Th1/Th2 ratios in the present SCH subjects might have a genetic basis because altered gene expression of various Th1/Th2 cytokines has been found in SCH, including IFN‐γ, TNF‐α, IL‐2, and IL‐4 . Genetic polymorphisms of distinct Th1/Th2 cytokines were also highly correlated with SCH, including IFN‐γ, TNF‐α, IL‐2, and IL‐10 . In addition, environmental factors such as viral infections could have caused the Th2 shift in the present SCH subjects because viral infections have been closely associated with SCHand often result in activation of the Th1/Th2 systems .…”

Section: Discussionmentioning

confidence: 81%

Is T‐helper type 2 shift schizophrenia‐specific? Primary results from a comparison of related psychiatric disorders and healthy controls

Chiang

Riedel²,

Schwarz³

et al. 2013

Psychiatry Clin Neurosci

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Aim: An imbalance between T-helper type 1 (Th1) and type 2 (Th2) cytokines has been implicated in schizophrenia, although empirical evidence is rare. The aim of this study was to examine if a Th1/Th2 imbalance occurs in schizophrenia and schizophrenia-related disorder.Methods: Twenty-six subjects with schizophrenia, 26 subjects with schizophrenia-related disorders, and 26 healthy controls were recruited. The Human Th1/Th2 Cytokine Cytometric Bead Array Kit-II was utilized to assess serum Th1/Th2 cytokines and ratios simultaneously. MANOVA was used to detect differences among the three diagnostic groups in distinct Th1/ Th2 cytokines/ratios. Pearson/Spearman correlations were used to examine the relationships between distinct Th1/Th2 cytokines/ratios and clinical/ psychopathological data in schizophrenia.Results: Interferon (IFN)-g/interleukin (IL)-4, IFN-g/ IL-10, IL-2/IL-4, and tumor necrosis factor (TNF)-a/IL-4 ratios were significantly decreased in schizophrenia, but not in schizophrenia-related disorders compared to healthy controls. IFN-g/IL-4 and IFN-g/ IL-10 in schizophrenia subjects positively correlated with age, but not in schizophrenia-related disorder subjects or in healthy controls. Conclusion:A clear Th2 shift was observed in schizophrenia, but not in schizophrenia-related disorders. The Th2 shift in schizophrenia appeared to be an aberrant developmental phenomenon.

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Section: Discussionmentioning

confidence: 81%

Is T‐helper type 2 shift schizophrenia‐specific? Primary results from a comparison of related psychiatric disorders and healthy controls

Chiang

Riedel²,

Schwarz³

et al. 2013

Psychiatry Clin Neurosci

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show abstract

“…In this context, it would be relevant to investigate effects of SNPs at transcription factor-binding sites to improve molecular knowledge of DNA/ protein interactions, even more so after the studies carried out on SNPs in exonic sequences which bring about no relevant modifications of enzyme functions [18,37,44]. Actually, very few SNPs are associated with pathological phenotypes [43,45,50,51]. Another aspect that should be analyzed is the relationships between transcriptional variants or their ratio of expression levels and functional/pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Bradford et al [49] genotyped eight SNPs of TGM2 gene representing intron variants associated with schizophrenia in a British cohort of patients; this suggests the relevance of the SNPs rs4811528, rs2076380, rs6023526 and rs7270785 in the modulation of TGM2 expression. Further studies demonstrated that rs4811528 SNP is also associated with raised levels of interleukin 2 (IL-2) in plasma, but without sufficient evidence to define this condition as a predisposing factor to develop schizophrenia [50].…”

Section: Selective Roles Of Tg2 In Different Cellular Locationsmentioning

confidence: 99%

Spotlight on the transglutaminase 2 gene: a focus on genomic and transcriptional aspects

Bianchi

Beninati

Bergamini

2018

Biochemical Journal

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The type 2 isoenzyme is the most widely expressed transglutaminase in mammals displaying several intra- and extracellular activities depending on its location (protein modification, modulation of gene expression, membrane signalling and stabilization of cellular interactions with the extracellular matrix) in relation to cell death, survival and differentiation. In contrast with the appreciable knowledge about the regulation of the enzymatic activities, much less is known concerning its inducible expression, which is altered in inflammatory and neoplastic diseases. In this context, we first summarize the gene's basic features including single-nucleotide polymorphism characterization, epigenetic DNA methylation and identification of regulatory regions and of transcription factor-binding sites at the gene promoter, which could concur to direct gene expression. Further aspects related to alternative splicing events and to ncRNAs (microRNAs and lncRNAs) are involved in the modulation of its expression. Notably, this important gene displays transcriptional variants relevant for the protein's function with the occurrence of at least seven transcripts which support the synthesis of five isoforms with modified catalytic activities. The different expression of the TG2 (type 2 transglutaminase) variants might be useful for dictating the multiple biological features of the protein and their alterations in pathology, as well as from a therapeutic perspective.

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Children with autism spectrum disorders (ASD) who exhibit chronic gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of peripheral blood (PB) monocytes

Jyonouchi

Geng

Streck

et al. 2011

Journal of Neuroimmunology

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The functional significance of the TGM2 gene in schizophrenia: A correlation of SNPs and circulating IL-2 levels

Cited by 4 publications

References 20 publications

Is T‐helper type 2 shift schizophrenia‐specific? Primary results from a comparison of related psychiatric disorders and healthy controls

Is T‐helper type 2 shift schizophrenia‐specific? Primary results from a comparison of related psychiatric disorders and healthy controls

Spotlight on the transglutaminase 2 gene: a focus on genomic and transcriptional aspects

Children with autism spectrum disorders (ASD) who exhibit chronic gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of peripheral blood (PB) monocytes

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