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Gene Review

GSTA1  -  glutathione S-transferase alpha 1

Homo sapiens

Synonyms: GST HA subunit 1, GST class-alpha member 1, GST-epsilon, GST2, GSTA1-1, ...
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Disease relevance of GSTA1

  • These results, although based on a small study population, describe an apparent difference in survival after treatment for breast cancer according to GSTA1 genotype [1].
  • CONCLUSIONS: These findings suggest that the GSTA1 and GSTT1 polymorphisms are associated with prostate cancer susceptibility, especially among smokers [2].
  • GSTP1 and GSTA1 polymorphisms interact with cruciferous vegetable intake in colorectal adenoma risk [3].
  • A stereological grid point counting method was used to estimate the percent of cells staining positive for GSTA1 in normal prostate, PIA, HGPIN, and adenocarcinoma [4].
  • The risk of colorectal cancer is associated not only with CYP2E1 high-activity alleles, but also GSTA1 low-activity alleles, among consumers of red or processed meat [5].

High impact information on GSTA1

  • The data suggest that the most active glutathione-S-transferases in liver are the products of two autosomal loci, GST1 and GST2 [6].
  • In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG [7].
  • Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (+/-2) weeks compared with controls (400% difference; 95% CI, 240%-734%; P < .001) [7].
  • GSTA1/A2 and GSTP1 were found to be the most abundant GSTs in human lung, being present in the bronchial and bronchiolar epithelium of all individuals studied [8].
  • This complex binds with extraordinary affinity to the active site of all these dimeric enzymes; GSTA1-1 shows the strongest interaction (KD congruent with 10-10 m), whereas GSTM2-2 and GSTP1-1 display similar and slightly lower affinities (KD congruent with 10-9 m) [9].

Chemical compound and disease context of GSTA1


Biological context of GSTA1


Anatomical context of GSTA1

  • The 3 cell lines which expressed GSTA1 were all erythroid [19].
  • This implies a greater cytoprotective role for GSTT1 and GSTA1 in erythroid cells and GSTM1 in lymphoid cells [19].
  • These consistent patterns of expression would suggest that compared to duodenum and small intestine, colon and to a lesser extent stomach always have low potential for GST-dependent detoxification of chemical carcinogens and are therefore at greater risk of genotoxic effects, particularly via substrates that are specific for GSTA1 [20].
  • Similarly, mean levels of hGSTA1 protein expression in liver cytosols decreased significantly according to genotype: hGSTA1*A > hGSTA1-heterozygous > hGSTA1*B [21].
  • HLE B-3 cell membranes were prepared, peroxidized, and used to examine whether hGSTA1-1 and hGSTA2-2 catalyzes the reduction of membrane PL-OOH in situ using the microiodometric and spectrophotometric assays [17].

Associations of GSTA1 with chemical compounds

  • Screening of the Alpha class glutathione transferases (GSTs) in the EST database identified 10 putative polymorphisms in the coding region of the GSTA1 and GSTA2 genes, six of which were subsequently verified by sequence analysis [15].
  • A recently described polymorphism alters hepatic expression of GSTA1, a GST with high activity in glutathione conjugation of metabolites of cyclophosphamide (CP) [1].
  • The prostate has potential for GSTP1-dependent detoxification of ATP-activated N-hydroxy-PhIP but little potential for detoxification of N-acetoxy-PhIP by GSTA1 [22].
  • Vmax/KM for GSTA1-1 was 7.95 microliters/min/mg protein, the highest busulfan-conjugating activity of all human liver and placenta isoforms evaluated [23].
  • Many of the cells within PIA lesions contain elevated levels of GSTP1, glutathione S-transferase-alpha (GSTA1), and cyclooxygenase-II proteins, suggesting a stress response [24].

Regulatory relationships of GSTA1


Other interactions of GSTA1


Analytical, diagnostic and therapeutic context of GSTA1

  • RT-PCR results verified a reduction in the expression of GSTA1 [29].
  • In this study we determined the frequencies of allelic variants of GSTA1 and GSTT1 in a Japanese population using PCR-restriction fragment length polymorphism and allele-specific PCR [30].
  • CONCLUSIONS: We have failed to demonstrate within the limitation of a case-control study a reproducible significant association of GST polymorphisms with susceptibility to ALD but there are suggestions that GSTA1 and GSTT1 warrant further study [31].
  • METHODS: We performed immunohistochemistry against GSTA1 on formalin-fixed radical prostatectomies (n = 45) [4].
  • The frequency of GSTA1 *A/*B or *B/*B genotype was 24.3% in urothelial cancer cases, compared with 21.2% in the control groups (OR=1.22; 95%CI 0.87-1.72) after adjustment for age, gender and smoking status [32].


  1. Association between a glutathione S-transferase A1 promoter polymorphism and survival after breast cancer treatment. Sweeney, C., Ambrosone, C.B., Joseph, L., Stone, A., Hutchins, L.F., Kadlubar, F.F., Coles, B.F. Int. J. Cancer (2003) [Pubmed]
  2. Human glutathione S-transferase A1, T1, M1, and P1 polymorphisms and susceptibility to prostate cancer in the Japanese population. Komiya, Y., Tsukino, H., Nakao, H., Kuroda, Y., Imai, H., Katoh, T. J. Cancer Res. Clin. Oncol. (2005) [Pubmed]
  3. GSTP1 and GSTA1 polymorphisms interact with cruciferous vegetable intake in colorectal adenoma risk. Tijhuis, M.J., Wark, P.A., Aarts, J.M., Visker, M.H., Nagengast, F.M., Kok, F.J., Kampman, E. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  4. GSTA1 expression in normal, preneoplastic, and neoplastic human prostate tissue. Parsons, J.K., Nelson, C.P., Gage, W.R., Nelson, W.G., Kensler, T.W., De Marzo, A.M. Prostate (2001) [Pubmed]
  5. Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility. Reszka, E., Wasowicz, W., Gromadzinska, J. Br. J. Nutr. (2006) [Pubmed]
  6. Biochemical genetics of glutathione-S-transferase in man. Board, P.G. Am. J. Hum. Genet. (1981) [Pubmed]
  7. Glutathione S-transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum. Dann, A.T., Kenyon, A.P., Seed, P.T., Poston, L., Shennan, A.H., Tribe, R.M. Hepatology (2004) [Pubmed]
  8. Immunohistochemical localization of glutathione S-transferases in human lung. Anttila, S., Hirvonen, A., Vainio, H., Husgafvel-Pursiainen, K., Hayes, J.D., Ketterer, B. Cancer Res. (1993) [Pubmed]
  9. The specific interaction of dinitrosyl-diglutathionyl-iron complex, a natural NO carrier, with the glutathione transferase superfamily: suggestion for an evolutionary pressure in the direction of the storage of nitric oxide. De Maria, F., Pedersen, J.Z., Caccuri, A.M., Antonini, G., Turella, P., Stella, L., Lo Bello, M., Federici, G., Ricci, G. J. Biol. Chem. (2003) [Pubmed]
  10. Human CD34+ cells do not express glutathione S-transferases alpha. Czerwinski, M., Kiem, H.P., Slattery, J.T. Gene Ther. (1997) [Pubmed]
  11. Glutathione S-transferase (GSTM1, GSTT1 and GSTA1) polymorphisms and outcomes after treatment for acute myeloid leukemia: pharmacogenetics in Southwest Oncology Group (SWOG) clinical trials. Weiss, J.R., Kopecky, K.J., Godwin, J., Anderson, J., Willman, C.L., Moysich, K.B., Slovak, M.L., Hoque, A., Ambrosone, C.B. Leukemia (2006) [Pubmed]
  12. Increased mutagenicity of 1,2-dibromo-3-chloropropane and tris(2,3-dibromopropyl)phosphate in Salmonella TA100 expressing human glutathione S-transferases. Simula, T.P., Glancey, M.J., Söderlund, E.J., Dybing, E., Wolf, C.R. Carcinogenesis (1993) [Pubmed]
  13. Effects of phenytoin on glutathione status and oxidative stress biomarker gene mRNA levels in cultured precision human liver slices. Gallagher, E.P., Sheehy, K.M. Toxicol. Sci. (2001) [Pubmed]
  14. Glutathione S-transferases as antioxidant enzymes: small cell lung cancer (H69) cells transfected with hGSTA1 resist doxorubicin-induced apoptosis. Sharma, A., Patrick, B., Li, J., Sharma, R., Jeyabal, P.V., Reddy, P.M., Awasthi, S., Awasthi, Y.C. Arch. Biochem. Biophys. (2006) [Pubmed]
  15. Polymorphism of human Alpha class glutathione transferases. Tetlow, N., Liu, D., Board, P. Pharmacogenetics (2001) [Pubmed]
  16. The role of human glutathione S-transferases (hGSTs) in the detoxification of the food-derived carcinogen metabolite N-acetoxy-PhIP, and the effect of a polymorphism in hGSTA1 on colorectal cancer risk. Coles, B., Nowell, S.A., MacLeod, S.L., Sweeney, C., Lang, N.P., Kadlubar, F.F. Mutat. Res. (2001) [Pubmed]
  17. Protection of HLE B-3 cells against hydrogen peroxide- and naphthalene-induced lipid peroxidation and apoptosis by transfection with hGSTA1 and hGSTA2. Yang, Y., Sharma, R., Cheng, J.Z., Saini, M.K., Ansari, N.H., Andley, U.P., Awasthi, S., Awasthi, Y.C. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  18. Interactions between sulforaphane and apigenin in the induction of UGT1A1 and GSTA1 in CaCo-2 cells. Svehlíková, V., Wang, S., Jakubíková, J., Williamson, G., Mithen, R., Bao, Y. Carcinogenesis (2004) [Pubmed]
  19. Glutathione S-transferase enzyme expression in hematopoietic cell lines implies a differential protective role for T1 and A1 isoenzymes in erythroid and for M1 in lymphoid lineages. Wang, L., Groves, M.J., Hepburn, M.D., Bowen, D.T. Haematologica (2000) [Pubmed]
  20. Interindividual variation and organ-specific patterns of glutathione S-transferase alpha, mu, and pi expression in gastrointestinal tract mucosa of normal individuals. Coles, B.F., Chen, G., Kadlubar, F.F., Radominska-Pandya, A. Arch. Biochem. Biophys. (2002) [Pubmed]
  21. Effect of polymorphism in the human glutathione S-transferase A1 promoter on hepatic GSTA1 and GSTA2 expression. Coles, B.F., Morel, F., Rauch, C., Huber, W.W., Yang, M., Teitel, C.H., Green, B., Lang, N.P., Kadlubar, F.F. Pharmacogenetics (2001) [Pubmed]
  22. Expression of cytochromes P450 and glutathione S-transferases in human prostate, and the potential for activation of heterocyclic amine carcinogens via acetyl-coA-, PAPS- and ATP-dependent pathways. Di Paolo, O.A., Teitel, C.H., Nowell, S., Coles, B.F., Kadlubar, F.F. Int. J. Cancer (2005) [Pubmed]
  23. Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Czerwinski, M., Gibbs, J.P., Slattery, J.T. Drug Metab. Dispos. (1996) [Pubmed]
  24. Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection. Nakayama, M., Bennett, C.J., Hicks, J.L., Epstein, J.I., Platz, E.A., Nelson, W.G., De Marzo, A.M. Am. J. Pathol. (2003) [Pubmed]
  25. Identification of cDNAs encoding two human alpha class glutathione transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-4. Board, P.G. Biochem. J. (1998) [Pubmed]
  26. Glutathione S-transferase phenotypes in relation to genetic variation and fruit and vegetable consumption in an endoscopy-based population. Tijhuis, M.J., Visker, M.H., Aarts, J.M., Peters, W.H., Roelofs, H.M., Camp, L.O., Rietjens, I.M., Boerboom, A.M., Nagengast, F.M., Kok, F.J., Kampman, E. Carcinogenesis (2007) [Pubmed]
  27. Sulforaphane and its glutathione conjugate but not sulforaphane nitrile induce UDP-glucuronosyl transferase (UGT1A1) and glutathione transferase (GSTA1) in cultured cells. Basten, G.P., Bao, Y., Williamson, G. Carcinogenesis (2002) [Pubmed]
  28. Comparative expression of two alpha class glutathione S-transferases in human adult and prenatal liver tissues. Gallagher, E.P., Gardner, J.L. Biochem. Pharmacol. (2002) [Pubmed]
  29. Increased sensitivity of Hep G2 cells toward the cytotoxicity of cisplatin by the treatment of piper betel leaf extract. Young, S.C., Wang, C.J., Hsu, J.D., Hsu, J.L., Chou, F.P. Arch. Toxicol. (2006) [Pubmed]
  30. Genetic analysis of glutathione S-transferase A1 and T1 polymorphisms in a Japanese population. Matsuno, K., Kubota, T., Matsukura, Y., Ishikawa, H., Iga, T. Clin. Chem. Lab. Med. (2004) [Pubmed]
  31. The role of polymorphisms of glutathione S-transferases GSTM1, M3, P1, T1 and A1 in susceptibility to alcoholic liver disease. Brind, A.M., Hurlstone, A., Edrisinghe, D., Gilmore, I., Fisher, N., Pirmohamed, M., Fryer, A.A. Alcohol Alcohol. (2004) [Pubmed]
  32. Human glutathion S-transferase A1 polymorphism and susceptibility to urothelial cancer in the Japanese population. Komiya, Y., Tsukino, H., Nakao, H., Kuroda, Y., Imai, H., Katoh, T. Cancer Lett. (2005) [Pubmed]
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