Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study

Pejovic-Milovancevic, Milica; Mandic-Maravic, Vanja; Ćorić, Vesna; Mitkovic-Voncina, Marija; Kostić, Milutin; Savić-Radojević, Ana; Ercegovac, Marko; Matić, Marija; Peljto, Amir; Lečić-Toševski, Dušica; Simić, Tatjana; Plješa-Ercegovac, Marija

doi:10.1093/labmed/lmw017

Cited by 19 publications

(9 citation statements)

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“…, ~ 70% in Eurasian populations) [ 6 – 12 ]. This deletion variant has been associated strongly with susceptibility to bladder cancer [ 13 ], multiple sclerosis [ 14 ] and early onset of severe mental disorders [ 15 ], among other diseases. However, why this deletion has been maintained in human populations remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Complex evolution of the GSTM gene family involves sharing of GSTM1 deletion polymorphism in humans and chimpanzees

et al. 2018

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BackgroundThe common deletion of the glutathione S-transferase Mu 1 (GSTM1) gene in humans has been shown to be involved in xenobiotic metabolism and associated with bladder cancer. However, the evolution of this deletion has not been investigated.ResultsIn this study, we conducted comparative analyses of primate genomes. We demonstrated that the GSTM gene family has evolved through multiple structural variations, involving gene duplications, losses, large inversions and gene conversions. We further showed experimentally that the GSTM1 was polymorphically deleted in both humans and also in chimpanzees, through independent deletion events. To generalize our results, we searched for genic deletions that are polymorphic in both humans and chimpanzees. Consequently, we found only two such deletions among the thousands that we have searched, one of them being the GSTM1 deletion and the other surprisingly being another metabolizing gene, the UGT2B17.ConclusionsOverall, our results support the emerging notion that metabolizing gene families, such as the GSTM, NAT, UGT and CYP, have been evolving rapidly through gene duplication and deletion events in primates, leading to complex structural variation within and among species with unknown evolutionary consequences.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4676-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Complex evolution of the GSTM gene family involves sharing of GSTM1 deletion polymorphism in humans and chimpanzees

et al. 2018

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“…[ 44 ] The fact that GSTT1 active genotype is a risk factor for SCZ has been confirmed in many previous studies. [ 35 , 37 , 49 ] In this study, the null genotype proportion of GSTT1 were 45.60% and 50.38% for SCZ patients and healthy individuals, respectively. The results indicated that GSTT1 could be a candidate gene for predisposing to SCZ in Chinese Han population.…”

Section: Discussionmentioning

confidence: 57%

“…The results of our study are supported by Raffa et al, [ 37 ] and they suggested that GSTT1 null genotype might decrease the risk of SCZ in Tunisian. However, Pejovic-Milovancevic et al [ 35 ] and Matsuzawa et al [ 50 ] have demonstrated that GSTT1 polymorphism is not associated with susceptibility to SCZ independently.…”

Section: Discussionmentioning

confidence: 99%

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Glutathione S-transferase gene polymorphisms (GSTT1 and GSTM1) and risk of schizophrenia

Zhang¹,

Yang²,

Liu³

et al. 2020

Medicine

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Schizophrenia (SCZ) is a chronic disability disorder related to oxidative stress. Glutathione S-transferase (GST) is a group enzyme that protects cells and tissues from oxidative stress damage. Among GSTs, GSTT1 and GSTM1 have well defined genetic polymorphisms. The purpose of our research was to explore the correlation between GSTT1 and GSTM1 polymorphism and SCZ risk in Chinese Han population. A total of 650 subjects (386 SCZ patients and 264 healthy individuals) were included in this case–control designed study. The GSTT1 and GSTM1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). We explored the relationship between these 2 polymorphisms and the risk of SCZ. We found that the GSTT1 null genotype had a protective effect on the development of SCZ [odds ratio (OR) = 0.601, 95% confidence interval (95% CI) = 0.412–0.986, P = .031]. We also found that the combination of null genotypes of the GSTT1 and GSTM1 genes was made at a lower risk of SCZ (OR = 0.452, 95% CI = 0.238–0.845, P = .028). However, we found no correction between Positive and Negative Syndrome Scale score (PANSS) and GSTM1, GSST1 genotypes in SCZ patients. Our finding revealed that GSTT1 null polymorphisms may be related to the reduced risk of SCZ in Chinese Han population, and this risk was further reduced with the combination of GSTT1 null polymorphisms and GSTM1 null polymorphisms.

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“…Previous studies revealed that the GSTM family of genes have critical roles in several cancer types. GSTM1 is highly polymorphic in humans and is associated with multiple cancer types, such as bladder and breast cancer, metabolic disorders and autoimmune diseases, as well as anticancer drugs response and resistance ( 28 ) GSTM1 deletion in humans was indicated to have a key role in bladder ( 29 ) and breast cancer ( 30 , 31 ), multiple sclerosis ( 32 ), severe early-onset mental disorders including schizophrenia-spectrum disorder, bipolar disorder with psychotic symptoms or first-episode psychosis ( 33 ) and acute myeloid leukemia ( 34 ). Csejtei et al ( 35 ) identified that GSTM1 may be a prognostic biomarker in clinical diagnostics as well as a potential therapeutic candidate in colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification and verification of the prognostic value of the glutathione S‑transferase Mu genes in gastric cancer

Chen

Wang

et al. 2020

Oncol Lett

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Gastric cancer (GC) is one of the most frequently diagnosed gastrointestinal cancer types in the world. Novel prognostic biomarkers are required to predict the progression of GC. Glutathione S-transferase Mu (GSTM) belongs to a family of phase II enzymes that have been implicated in a number of cancer types. However, the prognostic value of the GSTM genes has not been previously investigated in GC. The Cancer Genome Atlas (TCGA) was used to evaluate mRNA expression levels of GSTMs in GC tissue samples. Overall survival (OS) rates, hazard ratios (HRs) and 95% CIs were calculated using the Cox logistic regression model and Kaplan-Meier (KM) analysis was performed. In addition, the KM plotter online database was used to validate mRNA expression and the prognostic value of GSMT family members in patients with GC. To predict the function of GSTM genes in these patients, several bioinformatics tools, including the Database for Annotation, Visualization and Integrated Discovery, gene multiple association network integration algorithm, Search Tool for the Retrieval of Interacting Genes/Proteins, Gene Set Enrichment Analysis (GSEA), nomogram and genome-wide co-expression analysis were used. In the present study, high expression of GSTM5 was indicated to be strongly associated with lower OS in patients with GC, according to the TCGA and KM plotter online databases (HR=1.47, 95% CI: 1.06-2.04, P=0.021; and HR=1.69, 95% CI: 1.42-2.01, P=1.6x10-9 , respectively). The results from the GSEA and genome-wide co-expression analysis indicated that GSTM5 expression associated with several biological process terms, including 'adhesion', 'angiogenesis', 'apoptotic process', 'cell growth', 'proliferation', 'migration', 'Hedgehog signaling', 'MAPK signaling' and the 'TGF-β signaling pathway'. In conclusion, the present results indicated that GSTM5 may serve as a biomarker for GC prognosis and may be a potential therapeutic target for GC.

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Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study

Abstract: The GSTM1-null genotype might be associated with higher risk for early onset severe mental disorders.

Cited by 19 publications

References 45 publications

Complex evolution of the GSTM gene family involves sharing of GSTM1 deletion polymorphism in humans and chimpanzees

Complex evolution of the GSTM gene family involves sharing of GSTM1 deletion polymorphism in humans and chimpanzees

Glutathione S-transferase gene polymorphisms (GSTT1 and GSTM1) and risk of schizophrenia

Identification and verification of the prognostic value of the glutathione S‑transferase Mu genes in gastric cancer

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