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Glutathion-S-Transferase

RDB2090

Reverse hybridization kit for the determination of the polymorphism of Glutathion-S-Transferase (GST) M1 and T1


  

Clinic

Glutathione-S-transferases (GST) are a multigen family of enzymes involved in detoxification and, sometimes, activation of a wide variation of exogene and endogene substances. In human they make up to 4% of total soluble protein in liver and catalyze the conjugation of glutathion to numerous potentially genotoxic xenobiotics, including aliphatic heterocyclic radicals, epoxides and arene oxides. The enzymes detoxify carcinogenic polycyclic aromatic hydrocarbons and conjugate isothiocyanates by transducing them in less reactive and more water soluble products (1).

Six classes of enzymes have been described as a, µ, p, t, z, w (GST-A, -M, -P, -T, -Z, -O). Various polymorphisms of the GST genes can be found, which results in reduced activity of the GST enzymes. Subjects with different GST genotype may therefore have different susceptibilities to environmental exposures and may be unable to eliminate electrophilic carcinogenes as efficiently. This may increase the risk of somatic mutations leading to tumor formation (2).


GST-M1 and GST-T1 deletion genotypes

For GST-M1 and GST-T1 gene deletion genotypes are described and individuals with homozygous deletions of GST-M or GST-T (called null genotype) lack any functional GST-M1 or GST-T1 protein. The frequency of these null genotypes in the caucasian population is 50% for GST-M1 and about 20% for GST-T1. In various studies different associations between cancer and GST genotypes has been observed. Allthough interpretation of such studies is very difficult because of interactions in detoxification of large numbers of GST isozymes as well as other biotransforming enzymes like cytochromes P450 and N-Acetyltransferases. Beside of direct association with diseases the combination of both null-genotypes GST-M1 and GST-T1 was found to be associated with unresponsiveness to primary chemotherapy (3).

  

gluthation-S-transferase
 

References

  1. Eaton DL, Bammler TK. (1999)
    Concise review of the glutathione S-transferases and their significance to toxicology.
    Toxicol Sci. 49(2):156-64.

  2. Coughlin SS, Hall IJ. (2002)
    Glutathione S-transferase polymorphisms and risk of ovarian cancer: a HuGE review.
    Genet Med. 4(4):250-257. Review.


  3. Howells RE, Redman CW, Dhar KK, Sarhanis P, Musgrove C, Jones PW, Alldersea J, Fryer AA, Hoban PR, Strange RC. (1998)
    Association of glutathione S-transferase GSTM1 and GSTT1 null genotypes with clinical outcome in epithelial ovarian cancer.
    Clin Cancer Res. 4(10):2439-2445.

  4. Strange RC, Spiteri MA, Ramachandran S, Fryer AA. (2001)
    Glutathione-S-transferase family of enzymes.
    Mutat Res. 482(1-2):21-26. Review

  5. Hengstler JG, Kett A, Arand M, Oesch-Bartlomowicz B, Oesch F, Pilch H, Tanner B. (1998)
    Glutathione S-transferase T1 and M1 gene defects in ovarian carcinoma.
    Cancer Lett. 14;130(1-2): 43-48

  6. Zheng W, Wen WQ, Gustafson DR, Gross M, Cerhan JR, Folsom AR. (2002)
    GSTM1 and GSTT1 polymorphisms and postmenopausal breast cancer risk.
    Breast Cancer Res Treat.;74(1):9-16.

  7. Giannakopoulos X, Charalabopoulos K, Baltogiannis D, Chatzikiriakidou A, Alamanos Y, Georgiou I, Evangelou A, Agnantis N, Sofikitis N. (2002)
    The role of N-acetyltransferase-2 and glutathione S-transferase on the risk and aggressiveness of bladder cancer.
    Anticancer Res. 22(6B):3801-3804.16

  8. Nazar-Stewart V, Vaughan TL, Stapleton P, Van Loo J, Nicol- Blades B, Eaton DL. (2003)
    A population-based study of glutathione S-transferase M1, T1 and P1 genotypes and risk for lung cancer.
    Lung Cancer. 40(3):247-258.

  9. Rebbeck TR. (1997)
    Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility.
    Cancer Epidemiol Biomarkers Prev. 1997 Sep;6(9):733-743.

  10. Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB. (1994)
    Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism.
    Biochem J. May 15;300 ( Pt 1):271-276.

  
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  Pharmacogenetics
Cytochrom P450 CYP2C19
Cytochrom P450 CYP2C9 + VKORC1
Glutathion-S-Transferase
NAT-2


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