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Study of the association between glutathione S-transferase (GSTM1, GSTT1, GSTP1) polymorphisms with type II diabetes mellitus in southern of Iran

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Abstract

Diabetes Mellitus is characterized by chronic hyperglycemia and associated with an increased production of reactive oxygen species (ROS). Oxidative stress is the result of accumulation of free radicals in tissues which specially affects beta cells in pancreas. Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that include several classes of GSTs. These enzymes have important roles in decreasing of ROS species and act as a kind of antioxidant defense. To investigate the association between GSTs polymorphism with type 2 diabetes mellitus (T2DM), we investigated the frequency of GSTM1, T1 and P1 genotypes in patients with T2DM and controls. The genotypes of GSTT1, M1 and P1 were determined in 171 clinically documented T2DM patients and 169 normal cases (as controls) by multiplex polymerase chain reaction and PCR–RFLP. In diabetic patients, the frequency of GSTM1-null genotype was significantly (OR = 1.74; 95 % CI = 1.13–2.69, P = 0.016) higher than that in control. However, the frequency of GSTT1 (OR = 1.29; 95 % CI = 0.07–2.14, P = 0.367) and GSTP1 (OR = 0.83; 95 % CI = 0.53–1.30, P = 0.389) genotypes were not significantly different comparing both groups. Also, the frequency of both GSTT1-null and GSTM1-null genotypes in patients (19.88 %) was significantly higher compared to controls with the same genotypes (11.83 %, P = 0.022). Our results indicated that GSTM1 and GSTT1 genotypes might be involved in the pathogenesis of T2DM in south Iranian population.

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References

  1. World Health Organization (WHO) (2006) Diabetes mellitus fact sheet no. 312. Geneva

  2. Powers AC (2005) Diabetes mellitus. In: Braud E (ed) Harrison’s principles of internal medicine, 16th edn. McGraw Hill Medical Publishing Division, New York, pp 2152–2180

    Google Scholar 

  3. Whiting DR, Guariguata L, Weil C et al (2011) IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 94(3):311–321

    Article  PubMed  Google Scholar 

  4. http://www.emro.who.int/ncd/pdf/stepwise_saa_05.pdf

  5. http://www.who.int/chp/steps/2007STEPSreportIran.pdf

  6. Giron MD, Salto R, Gonzalez Y (1999) Modulation of hepatic and intestinal glutathione S-transferases and other antioxidant enzymes by dietary lipids in streptozotocin diabetic rats. Chemosphere 38:3003–3013

    Article  PubMed  CAS  Google Scholar 

  7. Opara EC (2002) Oxidative stress, micronutrients, diabetes mellitus and its complications. J R Soc Promot Health 122:28–34

    Article  CAS  Google Scholar 

  8. Friedlyand LE, Philipson LH (2005) Oxidative reactive species in cell injury: mechanism in diabetes mellitus and therapeutic approaches. Ann NY Acad Sci 1066:136–151

    Article  Google Scholar 

  9. West LC (2000) Radicals and oxidative stress in diabetes. Diabet Med 17:171–180

    Article  PubMed  CAS  Google Scholar 

  10. Robertson RP, Harmon J, Tran PO et al (2003) Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes 52:581–587

    Article  PubMed  CAS  Google Scholar 

  11. Niedowicz DM, Daleke DL (2005) The role of oxidative stress in diabetic complications. Cell 43:289–330

    CAS  Google Scholar 

  12. Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88

    Article  PubMed  CAS  Google Scholar 

  13. Matés J, Pérez-Gómez C, De Castro IN (1999) Antioxidant enzymes and human diseases. Clin Biochem 32(8):595–603

    Article  PubMed  Google Scholar 

  14. Qing-Yang H, Meng-Rong C, Sen-Lin JI (2006) Linkage and association studies of the susceptibility genes on type 2 diabetes. Acta Genetica Sinica 33(7):573–589

    Article  Google Scholar 

  15. Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. J Biol Chem 249(22):7130–7139

    PubMed  CAS  Google Scholar 

  16. Wilce MC, Parker MW (1994) Structure and function of glutathione S-transferases. Biochem Biophys Acta 1205:1–18

    Article  PubMed  CAS  Google Scholar 

  17. Armstrong RN (1997) Structure, catalytic mechanism, and evolution of the glutathione transferases. Chem Res Toxicol 10(1):2–18

    Article  PubMed  CAS  Google Scholar 

  18. Josephy PD (2010) Genetic variation in human glutathione S-transferase enzymes: significance for pharmacology and toxicology. Hum Genomics Proteomics 2010:876490

    Google Scholar 

  19. Jakoby WB, Ziegler DM (1990) The enzymes of detoxification. J Biol Chem 265(34):20715–20718

    PubMed  CAS  Google Scholar 

  20. Strange RC, Spiteri MA, Ramachandran S et al (2001) Glutathione-S-transferase family of enzymes. Mutat Res 482(1–2):21–26

    PubMed  CAS  Google Scholar 

  21. Mannervik B, Board PG, Hayes JD et al (2005) Nomenclature for mammalian soluble glutathione transferases. Methods Enzymol 401:1–8

    Article  PubMed  CAS  Google Scholar 

  22. Nebert DW, Vasiliou V (2004) Analysis of glutathione S-transferase (GST) family. Hum Genet 1:460–464

    CAS  Google Scholar 

  23. Xu SJ, Wang YP, Roa B et al (1998) Characterization of the human class mu Glutathione S-transferase gene cluster and the GSTM1 deletion. J Biol Chem 273:3517–3527

    Article  PubMed  CAS  Google Scholar 

  24. Landi S (2000) Mammalian class theta GST and differential susceptibility to carcinogenesis: a review. Mutat Res 463:247–283

    Article  PubMed  CAS  Google Scholar 

  25. Sprenger R, Schlagenhaufer R, Kerb R et al (2000) Characterization of glutathione S-transferase GSTT1 deletion: discrimination of all genotypes by polymerase chain reaction indicates a trimodular genotype phenotype correlation. Pharmacogenetics 10:557–565

    Article  PubMed  CAS  Google Scholar 

  26. Parl FF (2005) Glutathione S-transferase genotypes and cancer risk. Cancer Lett 221:123–129

    Article  PubMed  CAS  Google Scholar 

  27. Johnsson AS, Stenberg G, Widersten M et al (1998) Structure-activity relationships and thermal stability of human glutathione S-transferase M1 and P1-1 governed by the H-site residue 105. J Mol Biol 278:687–698

    Article  Google Scholar 

  28. Ali-Osman F, Akande O, Antoun G et al (1997) Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalysis activity of the encoded proteins. J Biol Chem 272(15):10004–10012

    Article  PubMed  CAS  Google Scholar 

  29. Yalin S, Hatungil R, Preek A (2007) Glutathione S-transferase gene polymorphisms in Turkish patients with diabetes mellitus. Cell Biochem Funct 25:509–513

    Article  PubMed  CAS  Google Scholar 

  30. Bid HK, Konwar R, Saxena M et al (2010) Association of glutathione S-transferase (GSTM1, T1 and P1) gene polymorphisms with type 2 diabetes mellitus in north Indian population. J Postgrad Med 56(3):176–181

    Article  PubMed  CAS  Google Scholar 

  31. Wang G, Zhang L, Li Q (2006) Genetic polymorphisms of GSTT1, GSTM1, and NQo1 genes and diabetes mellitus risk in Chinese population. Biochem Biophys Res commun 341:310–313

    Article  PubMed  CAS  Google Scholar 

  32. Nowier SR, Kashmri NK, Abdel-Rasool HA (2009) Association of type 2 diabetes mellitus and Glutathione S transferase (GSTM1 and GSTT1) genetic polymorphism. Res J Medicine Med Sci 4(2):181–188

    CAS  Google Scholar 

  33. Ramprasath T, Murugan PS, Prabakaran AD (2011) Potential risk modifications of GSTT1, GSTM1 and GSTP1 (glutathione S-transferases) variants and their association to CAD in patients with type 2 diabetes. Biochem Biophys Res Commun 47:49–53

    Article  Google Scholar 

  34. Amer MA, Ghattas MH, Abo-EIMatty DM et al (2011) Influence of glutathione S-transferase polymorphisms on type 2 diabetes mellitus risk. Genet Mol Res 10(4):1–9

    Article  Google Scholar 

  35. Yan H, Sun X, Den W, Fan X, Liu T (2006) GSTP1, GSTM1, and GSTT1 polymorphisms in Tibetan mountaineers. Biol Sport 23(3):303–311

    Google Scholar 

  36. Moussa SA (2008) Oxidative stress in Diabetes mellitus. Romanian J Biophys 18(3):225–236

    CAS  Google Scholar 

  37. Their R, Brüning T, Roose PH (2003) Markers of genetic susceptibility in human environmental hygiene and toxicology: the role of selected CYP, Nat and GST genes. Int J Environ Health 206:149–171

    Article  Google Scholar 

  38. Brondani Lde A, Assmann TS, Duarte GC et al (2012) The role of the uncoupling protein 1 (UCP1) on the development of obesity and type 2 diabetes mellitus. Arq Bras Endocrinol Metabol 56(4):215–225

    Article  PubMed  Google Scholar 

  39. Al-Serri A, Anstee QM, Valenti L et al (2012) The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case–control and intra-familial allele association studies. J Hepatol 56(2):448–454

    Article  PubMed  CAS  Google Scholar 

  40. Harrison DJ, Hubbard AL, MacMillan J et al (1999) Microsomal epoxide hydrolase gene polymorphism and susceptibility to colon cancer. Br J Cancer 79:168–171

    Article  PubMed  CAS  Google Scholar 

  41. Amirshahi P, Sunderland E, Farhud DD (1992) Population Genetics of the peoples of Iran I. Genetic polymorphisms of blood groups, serum proteins and red cell enzymes. Int J Antop 7:1–10

    Article  Google Scholar 

  42. Prokopenko I, McCarthy MI, Lindgren CM (2008) Type 2 diabetes: new genes, new understanding. Trends Gene 24(12):613–621

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to gratefully thank the staff of clinical diagnostic laboratory of Shahid Motahhari outpatients at Shiraz University of Medical Sciences. This work is the result of the M.Sc thesis which is done by Elham Moasser and supported by Shahid Chamran University of Ahvaz and Shiraz University of Medical Sciences.

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Authors and Affiliations

  1. Department of Genetics, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

    Elham Moasser & Seyed Reza Kazemi-Nezhad

  2. Department of biology, College of Sciences, Shiraz University, 71454, Shiraz, Iran

    Mostafa Saadat

  3. Organ Transplant Research Center, Nemazi Hospital, Shiraz University of Medical Sciences, Zand Street, 7193711351, Shiraz, Iran

    Elham Moasser & Negar Azarpira

Authors
  1. Elham Moasser
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  2. Seyed Reza Kazemi-Nezhad
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  3. Mostafa Saadat
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  4. Negar Azarpira
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Correspondence to Negar Azarpira.

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Moasser, E., Kazemi-Nezhad, S.R., Saadat, M. et al. Study of the association between glutathione S-transferase (GSTM1, GSTT1, GSTP1) polymorphisms with type II diabetes mellitus in southern of Iran. Mol Biol Rep 39, 10187–10192 (2012). https://doi.org/10.1007/s11033-012-1893-4

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  • DOI: https://doi.org/10.1007/s11033-012-1893-4

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