Frequency of GSTT1*0 genotype as a non-conjugator phenotype in a group of healthy Iranian people


Glutathione S-transferases (GSTs) are dimeric mainly cytosolic enzymes involved in detoxification of many exogenous and endogenous disease-causing electrophilic substrates. GSTs also have critical role in phase II biotransformation of a number of drugs, xenobiotics and industrial chemicals and protect cellular macromolecules. The evidences supported that human GSTT1 contributes in the deactivation of reactive oxygen species which more likely to be effective in inflammatory diseases, ageing and some non-cancer diseases also different types of cancers. The GSTT1 is genetically deleted in a high percentage of the different ethnic groups. Although this gene is highly conserved during evolution, it is indeed surprising that the GSTT1 deleted gene could be found in high incidence of human population. Conjugator and non-conjugator phenotypes are coincident with this deletion (GSTT1*1 and GSTT1*0 genotype).The consequences of this deletion could be involved in some diseases outcome, toxicology and drug resistances. In this study the Real-time PCR assay and a set of hybridization probes was used as a one-step and accurate method to estimate the frequency of GSTT1*0 genotype as a non-functional phenotype in 90 healthy individuals from the province of Isfahan in Iran. GSTT1 genotypes were identified in DNA samples using fluorogenic Real-Time PCR (LightCycler) followed by online melting curve analysis. The incidence of GSTT1*1(wild type) and GSTT1*0(Null type) were 74.5% and 25.5% respectively. No differences in genotypes frequencies were perceived in samples stratified by age and gender P> 0.05. The results were compared with other ethnic groups to get more insight into the frequency differences of defected carcinogens metabolizer gene due to deletion polymorphism of GSTT1. It has been indicated the incidence of GSTT1*0 in this group of Iran showed significant differences with East Asian and some European and American countries P< 0.05.The prevalence of GSTT1 null genotype in the study group from Isfahan province of Iran was slightly higher in comparison with other Iranian ethnic group (Iranian Georgian 15.7%), but this difference was not significant (χ2=1.66, P=0.197). Further experimental investigations are needed to inquiry the clinical implications of GSTT1 genetic polymorphism with consider to significant variability among different ethnicities.

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AghajanyNasab, M. , MirabSamiee, S. , Panjehpour, M. , Malekirad, A. and Movahedian-Attar, A. (2011) Frequency of GSTT1*0 genotype as a non-conjugator phenotype in a group of healthy Iranian people. Journal of Biomedical Science and Engineering, 4, 180-186. doi: 10.4236/jbise.2011.43025.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] MciIlwain, C.C., Townsed, D.M. and Tew, K.D. (2006) Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene, 25, 1639-1648. doi:10.1038/sj.onc.1209373
[2] Strange, R.C., Jones, P.W. and Fryer, A.A. (2000) Glutathione S-transferase genetics and role in toxicity. Toxicology Letters, 112, 357-363. doi:10.1016/S0378-4274(99)00230-1
[3] Wen, H. and Ali-osman, F. (2007) Genetic polymorphism and function of glutathione S-transferase in tumor drug resistance. Current Opinion in Pharmacology, 7, 367-374. doi:10.1016/j.coph.2007.06.009
[4] Jang, S.G., Kim, I.J. et al. (2007) GSTT2 promoter polymorphisms and colorectal cancer risk. BMC Cancer, 25, 7-16.
[5] Shewita, S.A. and Timisany, A.K. (2003) Cancer and Phase II drug-metabolizing enzymes. Current Drug Metabolism, 4, 45-58. doi:10.2174/1389200033336919
[6] Sivonova, M., Wakzuliva, I. et al. (2009) Polymorphisms of glutathione S-transferase M1, T1, P1 and the risk of prostate cancer. Journal of Experimental & Clinical Cancer Research, 5, 28-32.
[7] Zarte, R.R., Morales, R. et al. (2006) Potential application of GSTT1-null genotype in predicting toxicity associated to 5-fluouracil irinotecan and leucovorin regimen in advanced stage colorectal cancer patients. Oncology Reports, 16, 497-503.
[8] Giovanni, M. and Marco, M. (2007) Risk assessment of occupational exposure to polycyclic aromatic hydrocarbons by means of urinary1-hydroxypyrene. Toxicology and Industrial Health, 23, 55-59.
[9] Goodman, J.E. and Mechanic, L.E. (2006) Exploring “SNP-SNP interactions and colon cancer risk using polymorphism interaction analysis”. International Journal of Cancer, 118, 1790-1797.
[10] Norppa, H. (2004) Cytogenetics biomarkers. IARC Scientific Publications, 157, 179-205.
[11] Olvera-Bello, A.E. et al. (2010) Susceptibility to the cytogenetic effects of dichloromethane is related to the glutathione S-transferase theta phenotype. Toxicology Letters, 199, 218-224. doi:10.1016/j.toxlet.2010.09.002
[12] National Toxicology Program (2010) Final Report on Carcinogens Background Document for Formaldehyde. Final Report on Carcinogens Background Document, 10, i-512.
[13] Casanova, M., Bell, D.A. and Heck, H.A. (1997) Dichloromethane metabolism to formaldehyde and reaction with nucleic acids in hepatocytes of rodents and humans with and without glutathione S-transferase T1 and M1 genes. Fundamental and Applied Toxicology, 37, 168-180. doi:10.1006/faat.1997.2313
[14] Landi, S. (2000) Mammalian class theta GST and differential susceptibility to carcinogenesis: a review. Mutation Research, 463, 247-283. doi:10.1016/S1383-5742(00)00050-8
[15] Kezic, S. and Calkoen, F. (2006) Genetic polymorphism of metabolic enzymes modifies the risk of chronic solvent-induced encephalopathy. Toxicology and Industrial Health, 22, 281-289. doi:10.1177/0748233706070287
[16] National Toxicology Program (2008) Final Report on Carcinogens Background Document for Styrene. Final Report on Carcinogens Background Document, 8, i-398.
[17] Ko, K., Koch, B. et al. (2000) Rapid analysis of GSTM1, GSTT1, GSTP1 polymorphisms using real-time polymerase chain reaction. Pharmacogenetics, 10, 1-4. doi:10.1097/00008571-200004000-00009
[18] Light Cycler Fast Start DNA Master PlusHybProbe.
[19] Huang, M. and Wang, Y. (2007) Multiple genetic polymorphism of GSTP1 313AG, MDR1 3435CC, and MTHFR 677CC highly correlated with early relapse of breast cancer patients in Taiwan. Annals in Surgical Oncology, 15, 872-880. doi:10.1245/s10434-007-9719-7
[20] Deeken, J.F., Figg, W.D. et al. (2007) Toward individualized treatment: prediction of anticancer drug disposition and toxicity with pharmacogenetics. Anticancer Drugs, 18, 111-126. doi:10.1097/CAD.0b013e3280109411
[21] Bosch, T.M. (2008) Pharmacogenomics of drug-metabolizing enzymes and drug transporters in chemotherapy. Methods in Molecular Biology, 448, 63-76.
[22] Efferth, T. and Volm, M. (2005) Pharmacogenetic for individualized cancer chemotherapy. Pharmacology & Therapeutics, 107, 155-76.
[23] Ahmadi, A. and J?nsson, P. (2002) Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy. Toxicology and Industrial Health, 18, 289-296.
[24] Parl, F.F. (2005) Glutathione S-transferase genotypes and cancer risk. Cancer Letters, 221, 123-129. doi:10.1016/j.canlet.2004.06.016
[25] Rafiee, L., Saadat, I. and Saadat, M. (2010) Glutathione S-transferase genetic polymorphisms (GSTM1, GTT1 and GSTO2 in three Iranian populations. Molecular Biology Reports, 37, 155-158. doi:10.1007/s11033-009-9565-8
[26] Nelson, H.H., Wiencke, J.K. et al. (1995) Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta. Carcinogenesis, 16, 1243-1245. doi:10.1093/carcin/16.5.1243
[27] Naoe, T. and Takeyama, K. (2000) Analysis of the genetic polymorphism in NQ01, GSTM1, GSTT1, and CYP3A4 in 469 Japanese patients with therapy-related leukemia, meylodysplastic syndrome and the acute myeloid leukemia. Clinical Cancer Research, 6, 4091-4095.
[28] Cho, H., Lee, S. et al. (2005) GSTM1, GSTT1 and GSTP1 Polymorphism in the Korean population. Journal of Korean Medical Science, 20, 1089-1092. doi:10.3346/jkms.2005.20.6.1089
[29] Jang, S.S., Jung, C.Y. et al. (2003) The GSTT1 genotype as a marker for susceptibility to lung cancer in Korean female never smoker. Tuberculosis and Respiratory Diseases, 54, 485-494.
[30] Choe, S.C., Yun, K.J. et al. (2003) Prognostic potential of glutathione S-transferase M1 and T1 null genotypes for gastric cancer progression. Cancer Letters, 195, 169-175.
[31] Chen, C.L., Liu, Q. and Relling, M.W. (1996) Simultaneous characterization of glutathione S-transferase M1 and T1 polymorphisms by polymerase chain reaction in American whites and blacks. Pharmacogenetics, 6, 187-191. doi:10.1097/00008571-199604000-00005
[32] Nelson, H.H., Wiencke, J.K. et al. (1995) Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta. Carcinogenesis, 16, 1243-1245. doi:10.1093/carcin/16.5.1243
[33] Atalyi, E., Gunes, S. et al. (2009) CYP1A2, CYP2D6, GSTM1, GSTP1 and GSTT1 gene polymorphisms in patients with bladder cancer in Turkish population. International Urology and Nephrology, 41, 259-266. doi 10.1007/s11255-008-9444-6
[34] Arruda, V.R., Grignolli, C.E. et al. (1998) Prevalence of homozygosity for the deleted allele of glutathione S-transferase mu GSTM1 and theta GSTT1 among distinct ethnic groups from Brazil: relevance to environmental carcinogenesis?” Clinical Genetics, 54, 210-214.
[35] Gattas, G.J.F., Kato, M. et al. (2004) Ethnicity and glutathione S-transferase (M1, T1) polymprphisms in a Brazilian population. Brazilian Journal of Medical and Biological Research, 37, 451-458. doi:10.1590/S0100-879X2004000400002
[36] Raimondi, S., Paracchini, V. et al. (2006) Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review. American Journal of Epidemiology, 164, 1027-1042. doi:10.1093/aje/kwj321
[37] Liao, C., Cao, Y.F. et al. (2010) An updating meta- analysis of the glutathione S-transferaseT1 polymorphisms and colorectal cancer risk: a HuGE review. International Journal of Colorectal Disease, 25, 25-37. doi:10.1007/s00384-009-0805-0
[38] Wan, H.W., Zhou, Y. et al. (2010) Genetic polymorphism of glutathione S-transferase T1 and the risk of colorectal cancer: a meta-analysis. Cancer Epidemiology, 34, 66-72.
[39] Boccia, S., La, T.G. et al. (2006) Glutathione stransferase T1 status and gastric cancer risk: a meta-analysis of the literature. Mutagenesis, 21, 115-123. doi:10.1093/mutage/gel005
[40] Saadat, M. (2006) Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and Susceptibility to gastric cancer: a meta-analysis. Cancer Science, 97, 505-509. doi:10.1111/j.1349-7006.2006.00207.x
[41] Abdel-Rahman, S.Z., Anwar, W.A. et al. (1998) GSTM1 and GSTT1 genes are potential risk modifiers for bladder cancer. Cancer Detection and Prevention, 22, 129-138. doi:10.1046/j.1525-1500.1998.00934.x
[42] Grando, J.P. and Kuasne, H. (2009) Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer. Clinical and Experimental Medicine, 9, 21-28. doi:10.1007/s10238-008-0015-z
[43] Ha, Y.S., Yan, C. et al. (2010) GSTT1 as a prognosticator for recurrence and progression in patients with non-muscle invasive bladder cancer. Disease Markers, 29, 81-87.

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