| 1 | Psychiatry Res 2007 Sep 153: 87-91 |
|---|---|
| PMID | 17586054 |
| Title | Genetic polymorphism of glutathione S-transferase T1: a candidate genetic modifier of individual susceptibility to schizophrenia. |
| Abstract | schizophrenia is highly heritable, but the specific genes involved remain to be determined. A genome wide scan approach has indicated that human chromosome 22q11.2 potentially influences schizophrenia susceptibility. The gene encoding glutathione S-transferase T1 (GSTT1), which pertains to phase II biotransformation enzymes, was also mapped to the above-mentioned band. The present case-control study was performed on 292 (206 males, 86 females) in-patients with schizophrenia, and a total of 292 healthy blood donors matched to the patients according to age (+/-5 years) and gender as a control group. The patients were chronic cases. The patients were diagnosed as chronic schizophrenia according to structured clinical interview using the Structured Clinical Interview for DSM-IV (clinician version) to confirm and document DSM-IV diagnosis. The GSTT1 genotypes were determined using a PCR-based method. The GSTT1 null genotype was 17.8% and 33.9% in the patients and control groups, respectively. The GSTT1 null genotype was associated with a significantly reduced risk of developing schizophrenia. On the other word, the positive GSTT1 genotype significantly increased the risk of schizophrenia. The present finding indicated that GSTT1 is a candidate gene for susceptibility to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2009 Jan 150B: 86-94 |
| PMID | 18449862 |
| Title | Association study between the genetic polymorphisms of glutathione-related enzymes and schizophrenia in a Japanese population. |
| Abstract | Several lines of evidence suggest that oxidative stress plays a role in the pathogenesis of schizophrenia, and that glutathione (GSH) plays a crucial role in antioxidant defense mechanisms. In this study, we performed association studies between GSH-related genes (GSTM1, GSTP1, GSTO1, GSTT1, GSTT2, GPX1, and GCLM) and schizophrenia in a Japanese population. The overall distributions of the genotypes and alleles of each gene were not different between schizophrenic patients and controls. Subjects with residual-type schizophrenia showed different distributions in the analysis of GSTM1 genotype and in the combination analysis of GSTs, GPX1, and GCLM genotypes although the small sample size should be considered as a limitation of this study. In addition, our findings revealed that there were large ethnic differences in the genotype distributions of those GSH-related genes. The present study suggests that GSH-related genes may not play a major role in the pathogenesis of schizophrenia in a Japanese population. However, a dysregulation of GSH metabolism may be one of the vulnerability factors contributing to the development of a certain type of schizophrenia, and it is likely that the ethnic background should be considered in further study for those GSH-related genes. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2009 Jan 150B: 86-94 |
| PMID | 18449862 |
| Title | Association study between the genetic polymorphisms of glutathione-related enzymes and schizophrenia in a Japanese population. |
| Abstract | Several lines of evidence suggest that oxidative stress plays a role in the pathogenesis of schizophrenia, and that glutathione (GSH) plays a crucial role in antioxidant defense mechanisms. In this study, we performed association studies between GSH-related genes (GSTM1, GSTP1, GSTO1, GSTT1, GSTT2, GPX1, and GCLM) and schizophrenia in a Japanese population. The overall distributions of the genotypes and alleles of each gene were not different between schizophrenic patients and controls. Subjects with residual-type schizophrenia showed different distributions in the analysis of GSTM1 genotype and in the combination analysis of GSTs, GPX1, and GCLM genotypes although the small sample size should be considered as a limitation of this study. In addition, our findings revealed that there were large ethnic differences in the genotype distributions of those GSH-related genes. The present study suggests that GSH-related genes may not play a major role in the pathogenesis of schizophrenia in a Japanese population. However, a dysregulation of GSH metabolism may be one of the vulnerability factors contributing to the development of a certain type of schizophrenia, and it is likely that the ethnic background should be considered in further study for those GSH-related genes. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | J. Mol. Neurosci. 2009 Jun 38: 173-7 |
| PMID | 19148781 |
| Title | Genetic polymorphism of glutathione S-transferase T1 (GSTT1) and QT-interval in schizophrenia patients. |
| Abstract | Several antipsychotic agents are known to prolong the QT interval in a dose-dependent manner. The antipsychotic drugs are substrates of the phase I of biotransformation enzymes of cytochrome P450. In order to find the possible influence of polymorphism of GSTT1 (a member of class theta glutathione S-transferase) on rate-corrected QT interval (QTc) of schizophrenia patients, the present study was done. Forty-three schizophrenia in-patients participated in the study. The patients were diagnosed as chronic schizophrenia according to structured clinical interview using SCID-I (clinician version) to confirm and document DSM-IV diagnosis. Measurements of QT and RR intervals were recorded using a magnifying grid on lead II. The QTc was calculated according to Bazett's formula. Polymerase chain reaction-based method was used in order to determine the GSTT1 genotypes. Based on the fitted model of multiple linear regression analysis, QTc decreased in persons with positive GSTT1 genotype in comparison with the null genotype (beta = -0.328, t = -2.346, p = 0.024). Active genotype of GSTT1 decreased the QTc. Also, QTc was significantly associated with smoking status; it was decreased in smokers compared with nonsmokers (beta = -0.372, t = -2.372, p = 0.014). |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Psychiatry Res 2011 May 187: 454-6 |
| PMID | 21093063 |
| Title | Genetic polymorphisms of glutathione S-transferases GSTM1, GSTT1, GSTP1 and GSTA1 as risk factors for schizophrenia. |
| Abstract | Oxidative damage is thought to play a role in the predisposition to schizophrenia. We determined if the polymorphisms of the GSTP1, GSTM1, GSTT1 and GSTA1 genes, which affect the activity of these enzymes against oxidative stress, have a role as susceptibility genes for schizophrenia, analyzing 138 schizophrenic patients and 133 healthy controls. We found that the combination of the absence of GSTM1 gene with the of the GSTM1 gene with the polymorphism GSTA1*B/*B, and the presence of the GSTT1 gene, represents a risk factor for schizophrenia, indicating that the combination of different GST polymorphisms has a role in the predisposition to schizophrenia, probably affecting the capacity of the cell to detoxify the oxidized metabolites of catecholamines. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Psychiatry Res 2011 May 187: 454-6 |
| PMID | 21093063 |
| Title | Genetic polymorphisms of glutathione S-transferases GSTM1, GSTT1, GSTP1 and GSTA1 as risk factors for schizophrenia. |
| Abstract | Oxidative damage is thought to play a role in the predisposition to schizophrenia. We determined if the polymorphisms of the GSTP1, GSTM1, GSTT1 and GSTA1 genes, which affect the activity of these enzymes against oxidative stress, have a role as susceptibility genes for schizophrenia, analyzing 138 schizophrenic patients and 133 healthy controls. We found that the combination of the absence of GSTM1 gene with the of the GSTM1 gene with the polymorphism GSTA1*B/*B, and the presence of the GSTT1 gene, represents a risk factor for schizophrenia, indicating that the combination of different GST polymorphisms has a role in the predisposition to schizophrenia, probably affecting the capacity of the cell to detoxify the oxidized metabolites of catecholamines. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Neuron Glia Biol. 2011 May 7: 199-203 |
| PMID | 22874804 |
| Title | Analysis of glutathione S-transferase genes polymorphisms and the risk of schizophrenia in a sample of Iranian population. |
| Abstract | Glutathione S-transferases (GSTs) are major intracellular antioxidants, which, impaired in their function, are involved in the progress of schizophrenia (SCZ). The aim of this case-control study was to investigate the association between the polymorphism of glutathione S-transferases M1 (GSTM1), T1 (GSTT1), the glutathione S-transferase P1 gene (GSTP1) and SCZ. We isolated genomic DNA from peripheral blood of 93 individuals with SCZ and 99 healthy control subjects' genotypes analyzing them for GSTM1, GSTT1 and GSTP1 using polymerase chain reaction. The analysis of the gene-gene interaction between GSTs indicated that the magnitude of the association was greater for the combined AG/GSTT1 & GSTM1 genotypes (OR = 2.51; 95% CI: 1.13-5.63, P = 0.02). The AG and combined AG + GG genotypes of GSTP1 increased the risk of SCZ (OR = 1.83; 95% CI: 0.94-3.75 and OR = 1.71; 95% CI: 0.92-3.19, respectively). The genotypes of GSTT/NULL, NULL/GSTM and NULL/NULL increased the risk of SCZ (OR = 2.05; 95% CI: 0.9-4.74; OR = 2.0; 95% CI: 1.68-2.31; and OR = 1.8; 95% CI: 0.57-2.46, respectively). The present study supports previous data that suggest that impairment in the function of GSTs genes may increase the risk of SCZ. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Neuropsychiatr Dis Treat 2013 -1 9: 1683-98 |
| PMID | 24204153 |
| Title | Possible associations between antioxidant enzyme polymorphisms and metabolic abnormalities in patients with schizophrenia. |
| Abstract | This study investigated the possible association between common and potentially functional polymorphisms of antioxidant enzymes and metabolic abnormalities in patients with schizophrenia. The possible associations of the glutathione S-transferase (GST) M1 null and GSTT1 null genotypes, and the superoxide dismutase 2 (SOD2) Val16Ala polymorphism with the risks of being overweight and having metabolic syndrome were examined using a logistic regression analysis in 154 schizophrenic Japanese patients and 203 controls. Among smokers with schizophrenia, the risks of being overweight and having decreased high-density lipoprotein cholesterol were significantly higher in those with the GSTM1 null genotype than in those with the present genotype (odds ratio 3.20 and 3.15, P=0.03 and P=0.04, respectively), while among nonsmokers with schizophrenia, the risk of an abnormal waist circumference was lower in those with the GSTM1 null genotype (odds ratio 0.34, P=0.04). The risk of a decreased high-density lipoprotein cholesterol level was significantly higher in patients with the combined GSTM1 null and GSTT1 present genotypes than in those with the present genotypes of both genes (odds ratio 3.60, P<0.01). The SOD2 Val16Ala polymorphism was not associated with risk of metabolic abnormalities in either group. The present study suggests that the GSTM1 null genotype, in combination with smoking status or GSTT1 genotype, might be associated with the metabolic abnormalities in patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Neuropsychiatr Dis Treat 2013 -1 9: 1683-98 |
| PMID | 24204153 |
| Title | Possible associations between antioxidant enzyme polymorphisms and metabolic abnormalities in patients with schizophrenia. |
| Abstract | This study investigated the possible association between common and potentially functional polymorphisms of antioxidant enzymes and metabolic abnormalities in patients with schizophrenia. The possible associations of the glutathione S-transferase (GST) M1 null and GSTT1 null genotypes, and the superoxide dismutase 2 (SOD2) Val16Ala polymorphism with the risks of being overweight and having metabolic syndrome were examined using a logistic regression analysis in 154 schizophrenic Japanese patients and 203 controls. Among smokers with schizophrenia, the risks of being overweight and having decreased high-density lipoprotein cholesterol were significantly higher in those with the GSTM1 null genotype than in those with the present genotype (odds ratio 3.20 and 3.15, P=0.03 and P=0.04, respectively), while among nonsmokers with schizophrenia, the risk of an abnormal waist circumference was lower in those with the GSTM1 null genotype (odds ratio 0.34, P=0.04). The risk of a decreased high-density lipoprotein cholesterol level was significantly higher in patients with the combined GSTM1 null and GSTT1 present genotypes than in those with the present genotypes of both genes (odds ratio 3.60, P<0.01). The SOD2 Val16Ala polymorphism was not associated with risk of metabolic abnormalities in either group. The present study suggests that the GSTM1 null genotype, in combination with smoking status or GSTT1 genotype, might be associated with the metabolic abnormalities in patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | Gene 2013 Jan 512: 282-5 |
| PMID | 23107768 |
| Title | Relationship between GSTM1 and GSTT1 polymorphisms and schizophrenia: a case-control study in a Tunisian population. |
| Abstract | There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the pathophysiology of schizophrenia. The glutathione S-transferases (GSTs) forms one of the major detoxifying groups of enzymes responsible for eliminating products of oxidative stress. Interindividual differences observed in the metabolism of xenobiotics have been attributed to the genetic polymorphism of genes coding for enzymes involved in detoxification. Thus, in this study we investigated the association of glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) gene deletion polymorphisms and schizophrenia in a Tunisian population. A case-control study including 138 schizophrenic patients and 123 healthy controls was enrolled. The GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). No association was found between the GSTM1 genotype and schizophrenia, whereas the prevalence of the GSTT1 active genotype was significantly higher in the schizophrenic patients (57.2%) than in the controls (45.5%) with (OR=0.6, IC 0.37-0.99, p=0.039). Thus, we noted a significant association between schizophrenia and GSTT1 active genotype. Furthermore, the combination of the GSTM1 and GSTT1 null genotypes showed a non-significant trend to an increased risk of schizophrenia. The present finding indicated that GSTT1 seems to be a candidate gene for susceptibility to schizophrenia in at least Tunisian population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Gene 2013 Jan 512: 282-5 |
| PMID | 23107768 |
| Title | Relationship between GSTM1 and GSTT1 polymorphisms and schizophrenia: a case-control study in a Tunisian population. |
| Abstract | There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the pathophysiology of schizophrenia. The glutathione S-transferases (GSTs) forms one of the major detoxifying groups of enzymes responsible for eliminating products of oxidative stress. Interindividual differences observed in the metabolism of xenobiotics have been attributed to the genetic polymorphism of genes coding for enzymes involved in detoxification. Thus, in this study we investigated the association of glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) gene deletion polymorphisms and schizophrenia in a Tunisian population. A case-control study including 138 schizophrenic patients and 123 healthy controls was enrolled. The GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). No association was found between the GSTM1 genotype and schizophrenia, whereas the prevalence of the GSTT1 active genotype was significantly higher in the schizophrenic patients (57.2%) than in the controls (45.5%) with (OR=0.6, IC 0.37-0.99, p=0.039). Thus, we noted a significant association between schizophrenia and GSTT1 active genotype. Furthermore, the combination of the GSTM1 and GSTT1 null genotypes showed a non-significant trend to an increased risk of schizophrenia. The present finding indicated that GSTT1 seems to be a candidate gene for susceptibility to schizophrenia in at least Tunisian population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | Pharmacology 2014 -1 94: 179-82 |
| PMID | 25358668 |
| Title | Association of glutathione s-transferase gene methylation with risk of schizophrenia in an Iranian population. |
| Abstract | It has been believed that epigenetic changes play a critical role in schizophrenia through improper interaction between genome and environmental risk factors. The aim of this case-control study was to investigate the association of the promoter hypermethylation status of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase P1 (GSTP1) genes with the risk of schizophrenia. Methylation-specific PCR was used to estimate DNA methylation in the blood of 80 patients with schizophrenia and 71 healthy controls. Promoter hypermethylation analysis of GSTT and GSTP indicated a significant difference between individuals with methylated and unmethylated status [odds ratio (OR) = 0.339, 95% confidence interval (95% CI) = 0.14-0.8, p = 0.012 and OR = 0.308, 95% CI = 0.135-0.7, p = 0.005, respectively]. The present study supports the hypothesis that impairment in the promoter region of GSTT and GSTP genes by hypermethylation may increase the risk of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 13 | Int J Mol Sci 2015 -1 16: 19602-11 |
| PMID | 26295386 |
| Title | Genetic Polymorphisms of Glutathione-Related Enzymes (GSTM1, GSTT1, and GSTP1) and Schizophrenia Risk: A Meta-Analysis. |
| Abstract | The association between polymorphisms of glutathione-related enzyme (GST) genes and the risk of schizophrenia has been investigated in many published studies. However, their results were inconclusive. Therefore, we performed a meta-analysis to explore the association between the GSTM1, GSTT1, and GSTP1 polymorphisms and the risk of schizophrenia. Twelve case-control studies were included in this meta-analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Our meta-analysis results revealed that GSTM1, GSTT1, and GSTP1 polymorphisms were not related to risk of schizophrenia (p > 0.05 in each model). Further analyses based on ethnicity, GSTM polymorphism showed weak association with schizophrenia in East Asian population (OR = 1.314, 95% CI = 1.025-1.684, p = 0.031). In conclusion, our meta-analysis indicated the GSTM1 polymorphism may be the only genetic risk factor for schizophrenia in East Asian population. However, more meta-analysis with a larger sample size were needed to provide more precise evidence. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 14 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2015 Oct 168: 630-6 |
| PMID | 26175060 |
| Title | Associations of common copy number variants in glutathione S-transferase mu 1 and D-dopachrome tautomerase-like protein genes with risk of schizophrenia in a Japanese population. |
| Abstract | Oxidative-stress, genetic regions of interest (1p13 and 22q11), and common copy number variations (CNVs) may play roles in the pathophysiology of schizophrenia. In the present study, we confirmed associations between schizophrenia and the common CNVs in the glutathione (GSH)-related genes GSTT1, DDTL, and GSTM1 using quantitative real-time polymerase chain reaction analyses of 620 patients with schizophrenia and in 622 controls. No significant differences in GSTT1 copy number distributions were found between patient groups. However, frequencies of characterized CNVs and assumed gain alleles of DDTL and GSTM1 were significantly higher in patients with schizophrenia. In agreement with a previous report, the present data indicate that gains in the CNV alleles DDTL and GSTM1 are genetic risk factors in Japanese patients with schizophrenia, and suggest involvement of micro-inflammation and oxidative stress in the pathophysiology of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 15 | PLoS ONE 2015 -1 10: e0128643 |
| PMID | 26046920 |
| Title | Meta-Analysis-Based Preliminary Exploration of the Connection between ATDILI and Schizophrenia by GSTM1/T1 Gene Polymorphisms. |
| Abstract | Anti-tuberculosis drugs have some adverse effects such as anti-tuberculosis drug-induced liver injury (ATDILI) and mental disorders. The involvement of glutathione S-transferase (GST) genes in pathogenesis of ATDILI or schizophrenia (SCZ) has been reported. Therefore, GST genes may exemplify molecular connectors between ATDILI and SCZ. However, association studies of GSTM1/T1 polymorphisms with these two diseases have yielded conflicting results. After searching case-control association studies in PubMed, ISI Web of Science, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Chinese BioMedical Literature Database, we performed meta-analyses across a total of 20 published association studies on 3146 subjects for the association of GSTM1 and ATDILI, 2587 for the GSTT1-ATDILI association, 2283 for GSTM1-SCZ and 1116 for GSTT1-SCZ to test the associations of GSTM1/T1 polymorphisms with ATDILI and SCZ. The GSTM1 present genotype was significantly associated with decreased risks of ATDILI (risk ratio(RR): 0.81, 95% confidence interval (CI): 0.75-0.88, P < 0.0001) and SCZ (RR: 0.88, 95%CI: 0.80-0.96, P = 0.004) according to the fixed-effect model, while the GSTT1 present genotype was significantly associated only with a high risk of SCZ (RR: 1.17, 95%CI: 1.04-1.32, P = 0.01) according to both the random- and fixed-effect models, but not with ATDILI (P = 0.82) according to the fixed-effect model. Moreover, these significant results were supported with moderate evidence according to the Venice criteria. These results indicate that GSTM1 represents a genetic connection between ATDILI and SCZ, and suggest that ATDILI and SCZ may be co-occurring for the subjects with GSTM1 null genotype. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 16 | Lab Med 2016 Apr -1: -1 |
| PMID | 27114251 |
| Title | Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study. |
| Abstract | To examine glutathione S-transferase (GST) deletion polymorphisms in development of early-onset severe mental disorders, with the hypothesis that patients with GSTM1-null and GSTT1-null genotypes will develop psychotic disorders at a younger age. We identified GSTM1 and GSTT1 deletion polymorphisms by multiplex polymerase chain reaction (PCR) in 93 patients with early onset severe mental disorders and 278 control individuals. The diagnoses were confirmed by Schedule for Affective Disorders and schizophrenia for School-Age Children-Present and Lifetime Version and Schedule for Affective Disorders and schizophrenia-Life-Time Version (K-SADS-PL) interviews. Individuals with the GSTM1-null genotype were at 3.36-fold higher risk of developing early-onset severe mental disorders than carriers of a corresponding active genotype. The risk of those disorders was increased by 6.59-fold in patients with GSTM1-null/GSTT1-active genotype. Patients with the GSTM1-null genotype were at approximately 2-fold increased risk for developing early-onset schizophrenia-spectrum disorder (EOS), early-onset bipolar disorder (EOBD) with psychotic symptoms, or early-onset first-episode psychosis (EOFEP), compared with patients with the GSTM1-active genotype. The GSTM1-null genotype might be associated with higher risk for early onset severe mental disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |