The TGM2 gene is associated with schizophrenia in a British population

Bradford, Matilda; Law, Matthew H.; Stewart, Andrew X; Shaw, Duncan; Megson, Ian L.; Wei, Jun

doi:10.1002/ajmg.b.30813

Cited by 14 publications

(14 citation statements)

References 29 publications

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“…TGM2 has been shown to be important for several different cellular processes such as cytoskeleton stabilization, apoptosis, cell differentiation, cell adhesion, and even GTP-hydrolysing activity. TGM2 activity is also well known to be involved in celiac disease (CD), a chronic, auto-immune mediated, small-intestinal disorder characterized by inflammatory injury to the mucosa following ingestion of wheat gluten [40]. TGM2-specific antibodies are almost exclusively found in CD and are therefore used as a diagnostic indicator of CD [41].…”

Section: Discussionmentioning

confidence: 99%

Significant Association of Estrogen Receptor Binding Site Variation with Bipolar Disorder in Females

2012

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Major depression is nearly twice as prevalent in women compared to men. In bipolar disorder, depressive episodes have been reported to be more common amongst female patients. Furthermore, periods of depression often correlate with periods of hormonal fluctuations. A link between hormone signaling and these mood disorders has, therefore, been suggested to exist in many studies. Estrogen, one of the primary female sex hormones, mediates its effect mostly by binding to estrogen receptors (ERs). Nuclear ERs function as transcription factors and regulate gene transcription by binding to specific DNA sequences. A nucleotide change in the binding sequence might alter the binding efficiency, which could affect transcription levels of nearby genes. In order to investigate if variation in ER DNA-binding sequences may be involved in mood disorders, we conducted a genome-wide study of ER DNA-binding in patients diagnosed with major depression or bipolar disorder. Association studies were performed within each gender separately and the results were corrected for multiple testing by the Bonferroni method. In the female bipolar disorder material a significant association result was found for rs6023059 (corrected p-value = 0.023; odds ratio (OR) 0.681, 95% confidence interval (CI) 0.570–0.814), a single nucleotide polymorphism (SNP) placed downstream of the gene coding for transglutaminase 2 (TGM2). Thus, females with a specific genotype at this SNP may be more vulnerable to fluctuating estrogen levels, which may then act as a triggering factor for bipolar disorder.

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Section: Discussionmentioning

confidence: 99%

Significant Association of Estrogen Receptor Binding Site Variation with Bipolar Disorder in Females

2012

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“…Four single nucleotide polymorphisms (SNPs) present in the TGM2 gene were selected for genotyping, including rs2076380, rs7270785, rs4811528, and rs6023526, as these four SNPs were reported to be associated with schizophrenia in our previous study (Bradford et al, 2009). These four SNPs were genotyped by PCR-based restriction fragment length polymorphism analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, the expression of the TGM2 gene was upregulated in the anterior cingulate cortex of patients with schizophrenia (patent number: WO/2004/053157). Genetic analysis showed a strong association of the TGM2 gene with schizophrenia in a British population (Bradford et al, 2009), although a genome-wide association (GWA) study has failed to show an association signal at the TGM2 locus (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014). It is worth noting that the P-value of 5 × 10 -8 set in the GWA study of schizophrenia may inflate the type II errors.…”

Section: Introductionmentioning

confidence: 99%

Lack of genetic association of the TGM2 gene with schizophrenia in a Chinese population

Wang

Liu

Wang

et al. 2015

Psychiatric Genetics

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The gene coding for transglutaminase 2 (TGM2) has been reported to be associated with schizophrenia in a White population. The present study was then designed to replicate this initial finding in a Chinese population. A total of 428 individuals with schizophrenia and 555 control participants were recruited for genetic analysis. Four single nucleotide polymorphisms present in the TGM2 gene were selected for genotyping, including rs2076380, rs7270785, rs4811528, and rs6023526, by PCR-based restriction fragment length polymorphism analysis. None of these four single nucleotide polymorphisms genotyped showed an association with schizophrenia, although these 428 cases and 555 controls had 97% power to detect a disease association in small effect size (odds ratio=1.5). The present results did not support the TGM2 association with schizophrenia. It is thus possible that the TGM2 finding may have resulted from a random error of sampling.

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“…However, there is no direct evidence that these mutations contribute to the development of diabetes in these patients. In a British population eight non-coding SNPs across the TGM2 gene were genotyped and it was suggested that the detected variants were associated with schizophrenia and TGM2 may have a role in the development of this mental disease (Bradford et al 2009). In another study a major fraction of human protein coding genes was examined in breast and colorectal cancer (Sjöblom et al 2006) to determine the spectrum and extent of somatic mutations; TGM2 was one of the genes with a somatic mutation (Gly660Val).…”

Section: Snps In the Tgm2 Genementioning

confidence: 99%

Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions

2011

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Transglutaminase 2 (TG2) is a multifunctional member of an enzyme family: it modifies glutamine residues by cross-linking proteins and incorporating primary amines into them, has protein disulphide isomerase and protein kinase activities, mediates trans-membrane signal transduction and interactions between cell surface proteins and the extracellular matrix. These unusual multiple roles encoded into one polypeptide chain suggest that genomic variations in the TGM2 gene should be limited. Indeed, the available information in databases shows that unlike in the case of most other transglutaminases there are no common single nucleotide polymorphisms in exons of human TGM2. We collected data on and produced some of the rare genetic variants of TGM2 by site directed mutagenesis and found that some were less stable than the most abundant (wild type) enzyme variant and the majority had deficient transamidating activity. Further studies are required to clarify the pathologic significance of these rare TGM2 alleles in the human population.

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The TGM2 gene is associated with schizophrenia in a British population

Cited by 14 publications

References 29 publications

Significant Association of Estrogen Receptor Binding Site Variation with Bipolar Disorder in Females

Significant Association of Estrogen Receptor Binding Site Variation with Bipolar Disorder in Females

Lack of genetic association of the TGM2 gene with schizophrenia in a Chinese population

Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions

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