Genetic Polymorphism in Glutathione Transferases (GST): Population Distribution of GSTM1, T1, and P1 Conjugating Activity

Ginsberg, Gary; Smolenski, Susan; Hattis, Dale; Guyton, Kathryn Z.; Johns, Douglas O.; Sonawane, Babasaheb

doi:10.1080/10937400903158375

Cited by 121 publications

(89 citation statements)

References 176 publications

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“…The GST genes, especially GSTM1 (mu) and T1 (theta), are important since they present a deletion that results in impaired catalytic activity associated with greater sensitivity to toxic compounds. The homozygous deletion GSTM1 (M1 * 0) and GSTT1 (T1 * 0) genotypes are generally associated with a high risk of cancer and development of other diseases (Ginsberg et al 2009;Gundacker et al 2007;. However, there are few data with respect to the influence of GST polymorphisms on Hg detoxification in humans.…”

Section: Gst Polymorphisms and Methylmercury Metabolism 961mentioning

confidence: 99%

Evaluation of GlutathioneS-transferaseGSTM1andGSTT1Polymorphisms and Methylmercury Metabolism in an Exposed Amazon Population

Barcelos

Marco

Grotto

et al. 2012

Journal of Toxicology and Environmental Health, Part A

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Section: Gst Polymorphisms and Methylmercury Metabolism 961mentioning

confidence: 99%

Evaluation of GlutathioneS-transferaseGSTM1andGSTT1Polymorphisms and Methylmercury Metabolism in an Exposed Amazon Population

Barcelos

Marco

Grotto

et al. 2012

Journal of Toxicology and Environmental Health, Part A

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“…However, tissue abundance of various GST isoforms (including different GST genotypes) and GST isoform-selective substrates (Ginsberg et al, 2009) need to be further evaluated to develop scaling factors for reaction phenotyping using human recombinant GST isoforms.…”

Section: Relative Contribution Of Glutathione-s-transferasesmentioning

confidence: 99%

Evaluation of a New Molecular Entity as a Victim of Metabolic Drug-Drug Interactions--an Industry Perspective

Bohnert¹,

Patel²,

Templeton³

et al. 2016

Drug Metabolism and Disposition

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Under the guidance of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), scientists from 20 pharmaceutical companies formed a Victim Drug-Drug Interactions Working Group. This working group has conducted a review of the literature and the practices of each company on the approaches to clearance pathway identification (f CL ), estimation of fractional contribution of metabolizing enzyme toward metabolism (f m ), along with modeling and simulation-aided strategy in predicting the victim drug-drug interaction (DDI) liability due to modulation of drug metabolizing enzymes. Presented in this perspective are the recommendations from this working group on: 1) strategic and experimental approaches to identify f CL and f m , 2) whether those assessments may be quantitative for certain enzymes (e.g., cytochrome P450, P450, and limited uridine diphosphoglucuronosyltransferase, UGT enzymes) or qualitative (for most of other drug metabolism enzymes), and the impact due to the lack of quantitative information on the latter. Multiple decision trees are presented with stepwise approaches to identify specific enzymes that are involved in the metabolism of a given drug and to aid the prediction and risk assessment of drug as a victim in DDI. Modeling and simulation approaches are also discussed to better predict DDI risk in humans. Variability and parameter sensitivity analysis were emphasized when applying modeling and simulation to capture the differences within the population used and to characterize the parameters that have the most influence on the prediction outcome.

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“…As such, polymorphisms in genes encoding transporters, receptors, DNA repair enzymes, drug targets and genes involved in the metabolism of xenobiotics are the main causes of patient's heterogeneity [1]. Assessment of polymorphisms of these genes in different populations may explain, at least in part, the variation in response to cancer therapy and to toxic chemicals.…”

Section: Introductionmentioning

confidence: 99%

“…Glutathione S-transferases (GSTs) are a class of phase II enzymes present in many tissues, and are involved in xenobiotic detoxification, and thus contribute to the protection from broad range of compounds including carcinogens, chemotherapeutic agents, and en-vironmental pollutants [1,2]. Five classes of GST enzymes were described in humans: Alpha (α), Mu (μ), Pi (π), Zeta (ζ) and Theta (θ), with one or more genes in each class.…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphism of the Glutathione S-Transferase M1 and T1 Genes in Three Distinct Arab Populations

et al. 2011

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Abstract. Deletion polymorphisms for the glutathione S-transferase (GST) gene are associated with increased risk of cancer, and are implicated in detoxifying mutagenic electrophilic compounds. GST Polymorphic variants were reported for different populations. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 null genotypes among Bahraini, Lebanese and Tunisian Arabs. GST genotyping was done by multiplex PCR-based methods. Study subjects comprised 167 Bahrainis, 141 Lebanese and 186 Tunisians unrelated healthy individuals. GSTM1 deletion homozygosity of 49.7%, 52.5% and 63.4% were recorded for Bahraini, Lebanese and Tunisians, respectively. Among Bahrainis, the prevalence of GSTT1 null homozygotes was 28.7%, while in higher rates were seen in Lebanese (37.6%) and Tunisians (37.1%). Our results indicate that there are no major differences in allelic distribution of GSTM1 and GSTT1 genes between the three Arab populations investigated except between Bahrainis and Tunisians regarding the allelic distribution of GSTM1 gene (P = 0.013). Combined analysis of both genes revealed that 14.4% of Bahrainis, 16.3% of Lebanese and 21.0% of Tunisians harbor the deleted genotype of both genes. This is the first study that addresses GST gene polymorphism in Bahraini and Lebanese Arabs, and will help genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and drug effects in Arab populations.

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Genetic Polymorphism in Glutathione Transferases (GST): Population Distribution of GSTM1, T1, and P1 Conjugating Activity

Cited by 121 publications

References 176 publications

Evaluation of GlutathioneS-transferaseGSTM1andGSTT1Polymorphisms and Methylmercury Metabolism in an Exposed Amazon Population

Evaluation of GlutathioneS-transferaseGSTM1andGSTT1Polymorphisms and Methylmercury Metabolism in an Exposed Amazon Population

Evaluation of a New Molecular Entity as a Victim of Metabolic Drug-Drug Interactions--an Industry Perspective

Genetic Polymorphism of the Glutathione S-Transferase M1 and T1 Genes in Three Distinct Arab Populations

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