GST Theta null genotype is associated with an increased risk for ulcerative colitis: a case–control study and meta-analysis of GST Mu and GST Theta polymorphisms in inflammatory bowel disease

Broekman, Mark; Bos, Caro; Morsche, R.H.M. te; Hoentjen, Frank; Roelofs, Hennie M.J.; Peters, Wilbert H.M.; Wanten, Geert; Jong, Dirk J. de

doi:10.1038/jhg.2014.77

Cited by 12 publications

(14 citation statements)

References 31 publications

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“…6 Of the members of GSTs, glutathione S-transferase theta 1 (GSTT1), and GSTM1 in particular have become a recent target of active investigation into their role in increased susceptibility to IBD, Behçet's disease (BD), or other autoimmune diseases such as primary sclerosing cholangitis when either of the two GSTTs lose their function. 2,7,8 Deletion of the GSTT1 gene, a 50 kb genomic sequence containing the entire gene located on chromosome 22q11.2, results in a GSTT1-null genotype, 5,9 fails protein synthesis, and can decrease the ability to detoxify damaging compounds. 10 The GSTT1 null genotype leads to the absence of a functional GSTT1 enzyme 9,11 and results in increased susceptibility to a number of diseases, including IBD.…”

Section: Introductionmentioning

confidence: 99%

Glutathione S‐transferase theta 1 protects against colitis through goblet cell differentiation via interleukin‐22

et al. 2020

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The enzyme glutathione S‐transferase theta 1 (GSTT1) is involved in detoxifying chemicals, including reactive oxygen species (ROS). Here, we provide a significant insight into the role of GSTT1 in inflammatory bowel disease (IBD). We identified decreased expression of GSTT1 in inflamed colons from IBD patients compared to controls. We intrarectally or intraperitoneally delivered Gstt1 gene to mice with dextran sodium sulfate (DSS)‐induced colitis and noted attenuation of colitis through gene transfer of Gstt1 via an IL‐22 dependent pathway. Downregulation of GSTT1 by pathogen‐associated molecular patterns (PAMPs) of microbes reduced innate defense responses and goblet cell differentiation. The GSTT1 mutation in intestinal epithelial cells (IECs) and IBD patients decreased its dimerization, which was connected to insufficient phosphorylation of signal transducer and activator of transcription‐3 and p38/mitogen‐activated protein kinase by their common activator, IL‐22. GSTT1 ameliorated colitis and contributed as a modulator of goblet cells through sensing pathogens and host immune responses. Its mutations are linked to chronic intestinal inflammation due to its insufficient dimerization. Our results provide new insights into GSTT1 mutations that are linked to chronic intestinal inflammation due to its insufficient dimerization and their functional consequences in IBDs.

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Section: Introductionmentioning

confidence: 99%

Glutathione S‐transferase theta 1 protects against colitis through goblet cell differentiation via interleukin‐22

et al. 2020

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“…Regarding GSTT1 / M1 genes, both homozygous GSTT1 and GSTM1 deletion polymorphisms were shown to be associated with UC in Central China ( Ye et al, 2011 ), northern India ( Mittal et al, 2007 ), and in Turkish population ( Buyukgoze et al, 2013 ). Conversely, studies in Denmark ( Ernst et al, 2010 ) and Holland ( Broekman et al, 2014 ) as well as in Israeli Jews ( Karban et al, 2011 ) failed to demonstrate any relationship between GSTT1 / M1 loci and the risk of UC. Likewise, the GSTP1 rs1695 polymorphism showed significant association with UC in Central China ( Ye et al, 2011 ) and no association in Denmark ( Ernst et al, 2010 ).…”

Section: Discussionmentioning

confidence: 97%

Polymorphisms of glutathione S-transferase and methylenetetrahydrofolate reductase genes in Moldavian patients with ulcerative colitis: Genotype-phenotype correlation

et al. 2016

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BackgroundGlutathione S-transferases (GSTM1, GSTT1, and GSTP1) and methylenetetrahydrofolate reductase (MTHFR) are important enzymes for protection against oxidative stress. In addition, MTHFR has an essential role in DNA synthesis, repair, and methylation. Their polymorphisms have been implicated in the pathogenesis of ulcerative colitis (UC). The aim of the present study was to investigate the role of selected polymorphisms in these genes in the development of UC in the Moldavian population.MethodsIn a case-control study including 128 UC patients and 136 healthy individuals, GSTM1 and GSTT1 genotypes (polymorphic deletions) were determined using multiplex polymerase chain reaction (PCR). The GSTP1 rs1695 (Ile105Val), MTHFR rs1801133 (C677T), and MTHFR rs1801131 (A1298C) polymorphisms were studied with restriction fragment length polymorphism (RFLP) analysis. Genotype–phenotype correlations were examined using logistic regression analysis.ResultsNone of the genotypes, either alone or in combination, showed a strong association with UC. The case-only sub-phenotypic association analysis showed an association of the MTHFR rs1801133 polymorphism with the extent of UC under co-dominant (p corrected = 0.040) and recessive (p corrected = 0.020; OR = 0.15; CI = 0.04–0.63) genetic models. Also, an association between the MTHFR rs1801131 polymorphism and the severity of UC was reported for the over-dominant model (p corrected = 0.023; coefficient = 0.32; 95% CI = 0.10–0.54).ConclusionThe GST and MTHFR genotypes do not seem to be a relevant risk factor for UC in our sample. There was, however, evidence that variants in MTHFR may influence the clinical features in UC patients. Additional larger studies investigating the relationship between GST and MTHFR polymorphisms and UC are required.

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“…As a result, 16 individual studies from 11 publications were included in the analysis. These studies involved a total of 3366 cases and 6013 controls [17-24, 32-34]. The main characteristics of the 16 included studies in our meta-analysis are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…There were 146 studies excluded after reviewing the abstracts and full texts. Thus, 11 publications were included in the meta-analysis [17-24, 32-34]. There were five publications that assessed the association of the GSTT1 null genotype with CD and five publications for UC.…”

Section: Resultsmentioning

confidence: 99%

Glutathione S-Transferase T1 Null Genotype is Associated with Susceptibility to Inflammatory Bowel Disease

Qian¹,

Song

et al. 2017

Cell Physiol Biochem

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Background: The published literature contains conflicting results regarding the impact of the glutathione S-transferase T1 (GSTT1) null genotype on the susceptibility to inflammatory bowel disease. Therefore, we conducted a meta-analysis of observational studies to assess the association. Methods: We searched four online databases for eligible studies. The odds ratio (OR) with 95% CI was used to assess the gene-disease association. We also performed subgroup analyses by type of inflammatory bowel disease and ethnicity. Results: There were 16 individual studies from 11 publications included in the analysis. There were 3366 cases with inflammatory bowel disease and 6013 controls. The meta-analysis of all 16 studies showed the GSTT1 null genotype was associated with increased susceptibility to inflammatory bowel disease (OR = 1.98, 95%CI 1.39-2.84, P < 0.001). The subgroup analysis by ethnicity further identified an association between the GSTT1 null genotype and inflammatory bowel disease in Caucasians, Asians, and Africans. The GSTT1 null genotype was associated with both ulcerative colitis (OR = 1.96, P = 0.004) and Crohn’s disease (OR = 2.01, P = 0.022). The GSTT1 null genotype was still significantly associated with ulcerative colitis (OR = 1.63, P < 0.0001) and Crohn’s disease (OR = 1.40, P = 0.023) after adjusting for study heterogeneity. Conclusion: The GSTT1 null genotype is significantly associated with an increased susceptibility to inflammatory bowel disease and is a risk factor for both ulcerative colitis and Crohn’s disease.

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GST Theta null genotype is associated with an increased risk for ulcerative colitis: a case–control study and meta-analysis of GST Mu and GST Theta polymorphisms in inflammatory bowel disease

Cited by 12 publications

References 31 publications

Glutathione S‐transferase theta 1 protects against colitis through goblet cell differentiation via interleukin‐22

Glutathione S‐transferase theta 1 protects against colitis through goblet cell differentiation via interleukin‐22

Polymorphisms of glutathione S-transferase and methylenetetrahydrofolate reductase genes in Moldavian patients with ulcerative colitis: Genotype-phenotype correlation

Glutathione S-Transferase T1 Null Genotype is Associated with Susceptibility to Inflammatory Bowel Disease

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