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GSTT1 and GSTM1 gene polymorphisms in European and African populations

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Abstract

Glutathione S-transferases (GSTs) are a superfamily of detoxificant enzymes. Pharmacogenomic studies have revealed interethnic differences in GST allelic frequencies. This study is focused on GSTT1 (gene deletion, rs17850155, rs2234953, and rs11550605) and GSTM1 (gene deletion) gene frequency distributions in two population samples of Europe origin (Italy, n = 120; Spain, n = 94) and two population samples of Africa origin (Cameroon, n = 126; Ethiopia, n = 153). Detection of GSTT1 and GSTM1 null genotypes was performed by multiplex PCR analysis, while the other GSTT1 gene polymorphisms were detected using allele specific PCR and sequencing. GSTT1 and GSTM1 null frequencies in the samples analyzed fit with the variability range observed in European and African populations, respectively. The SNP analysis in GSTT1 gene did not highlight any nucleotide substitution in 493 individuals analyzed. The comparisons among GSTM1 and GSTT1 null phenotype frequencies in worldwide populations show different patterns between Asians, Africans, and Europeans. Important insights into the effects of GSTM1 and GSTT1 gene deletions on the pathogenesis of human diseases have been hypothesized. Detailed studies on the geography of GST variants could therefore increase knowledge about the relationship between ethnicity and the prevalence of certain diseases.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Barrett JC, Vainio H, Peakall D, Goldstein BD (1997) 12th meeting of the scientific group on methodologies for the safety evaluation of chemicals: susceptibility to environmental hazards. Environ Health Perspect 105:599–637

    Google Scholar 

  3. Perera FP (1997) Environment and cancer: who are susceptible? Science 278:1068–1073

    Article  CAS  PubMed  Google Scholar 

  4. Oliveira E, Marsh S, van Booven, Amorim A, Prata MJ, McLeod HL (2007) Pharmacogenetically relevant polymorphisms in Portugal. Pharmacogenomics 8:703–712

  5. Magno LA, Talbot J, Talbot T, Borges Santos AM, Souza RP, Marin LJ, Moreli ML, de Melo PRS, Corrêa RX, Santos FR, Di Pietro G (2009) Glutathione S-Transferase variants in a Brazilian population. Pharmacology 83:231–236

    Article  CAS  PubMed  Google Scholar 

  6. Kelada SN, Eaton DL, Wang SS, Rothman NR, Khoury MJ (2003) The role of genetic polymorphism in environmental health. Environ Health Perspect 111:1055–1064

    Article  CAS  PubMed  Google Scholar 

  7. Frova C (2006) Glutathione transferases in the genomics era: New insights and perspectives. Biomol Eng 23:149–169

    Article  CAS  PubMed  Google Scholar 

  8. McIlwain CC, Townsend DM, Tew KD (2006) Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene 25:1639–1648

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  10. Matsuno K, Kubota T, Matsukura Y, Ishikawa H, Iga T (2004) Genetic analysis of glutathione S-transferase A1 and T1 polymorphisms in a Japanese population. Clin Chem Lab Med 42:560–562

    Article  CAS  PubMed  Google Scholar 

  11. Budowle B, Moretti T, Smith J, Dizinno J (2000) DNA typing protocols: Molecular Biology and Forensic analysis. Bio Techniques® Books Publication, Eaton Publishing, Natick

    Google Scholar 

  12. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  CAS  PubMed  Google Scholar 

  13. Abdel-Rahman SZ, El-Zein RA, Anwar WA, Au WW (1996) A multiplex PCR procedure for polymorphic analysis of GST M1 and GST T1 genes in population studies. Cancer Lett 107:229–233

    Article  CAS  PubMed  Google Scholar 

  14. Alexandrie AK, Rannug A, Juronen E, Tasa G, Warholm M (2002) Detection and characterization of a novel functional polymorphism in the GSTT1 gene. Pharmacogenetics 12:613–619

    Article  CAS  PubMed  Google Scholar 

  15. Greenacre M (1992) Correspondence analysis in medical research. Stat Methods Med Res 1:97–117

    Article  CAS  PubMed  Google Scholar 

  16. Moyer AM, Salavaggione OE, Hebbring SJ, Moon I, Hildebrandt MAT, Eckloff BW, Schaid DJ, Wieben ED, Weinshilboum RM (2007) Glutathione S-transferase T1 and M1: gene sequence variation and functional genomics. Clin Cancer Res 13:7207–7216

    Article  CAS  PubMed  Google Scholar 

  17. Fuciarelli M, Caccuri A, De Francesca M, Ferazzoli F, Piacentini S, Porreca F (2009) Modulation of the GSTT1 activity by the GSTM1 phenotype in a sample of Italian farm-workers. Arch Toxicol 83:115–120

    Article  CAS  PubMed  Google Scholar 

  18. Bolt HM, Their R (2006) Relevance of the deletion polymorphisms of the Glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology. Curr Drug Metab 7:613–628

    Article  CAS  PubMed  Google Scholar 

  19. Gundacker C, Komarnicki G, Jagiello P, Gencikova A, Dahmen N, Wittmann KJ, Gencik M (2007) Glutathione-S-transferase polymorphism, metallothionein expression, and mercury levels among students in Austria. Sci Total Environ 385:37–47

    Article  CAS  PubMed  Google Scholar 

  20. Gattás GJ, Kato M, Soares-Vieira JA, Siraque MS, Kohler P, Gomes L, Rego MA, Bydlowski SP (2004) Ethnicity and glutathione S-transferase (GSTM1/GSTT1) polymorphisms in a Brazilian population. Braz J Med Biol Res 37:451–458

    Article  PubMed  Google Scholar 

  21. Liu L, Li C, Gao J, Li K, Gao L, Gao T (2009) Genetic polymorphisms of glutathione S-transferase and risk of vitiligo in the Chinese population. J Invest Dermatol 129:2646–2652

    Article  CAS  PubMed  Google Scholar 

  22. Buchard A, Sanchez JJ, Dalhoff K, Morling N (2007) Multiplex PCR detection of GSTM1, GSTT1, and GSTP1 gene variants: simultaneously detecting GSTM1 and GSTT1 gene copy number and the allelic status of the GSTP1 Ile105Val genetic variant. J Mol Diagn 9:612–617

    Article  CAS  PubMed  Google Scholar 

  23. Hamdy SI, Hiratsuka M, Narahara K, Endo N, El-Enany M, Moursi N, Ahmed MS, Mizugaki M (2003) Genotype and allele frequencies of TPMT, NAT2, GST, SULT1A1 and MDR-1 in the Egyptian population. Br J Clin Pharmacol 55:560–569

    Article  CAS  PubMed  Google Scholar 

  24. Abbas A, Delvinquiere K, Lechevrel M, Lebailly P, Gauduchon P, Launoy G, Sichel F (2004) GSTM1, GSTT1, GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population: different pattern of squamous cell carcinoma and adenocarcinoma. World J Gastroenterol 10:3389–3393

    CAS  PubMed  Google Scholar 

  25. Kiran M, Chawla YK, Kaur J (2008) Glutathione-S-transferase and microsomal epoxide hydrolase polymorphism and viral-related hepatocellular carcinoma risk in India. DNA Cell Biol 27:687–694

    Article  CAS  PubMed  Google Scholar 

  26. Rafiee L, Saadat I, Saadat M (2010) Glutathione S-transferase genetic polymorphisms (GSTM1, GSTT1 and GSTO2) in three Iranian populations. Mol Biol Rep 37:155–158

    Article  CAS  PubMed  Google Scholar 

  27. Fujihara J, Yasuda T, Iida R, Takatsuka H, Fujii Y, Takeshita H (2009) Cytochrome P450 1A1, glutathione S-transferases M1 and T1 polymorphisms in Ovambos and Mongolians. Leg Med (Tokyo) Suppl 1:S408–S410

    Google Scholar 

  28. Uhm YK, Yoon SH, Kang IJ, Chung JH, Yim SV, Lee MH (2007) Association of glutathione S-transferase gene polymorphisms (GSTM1 and GSTT1) of vitiligo in Korean population. Life Sci 1:223–227

    Article  Google Scholar 

  29. Montero R, Araujo A, Carranza P, Mejía-Loza V, Serrano L, Albores A, Salinas JE, Camacho-Carranza R (2007) Genotype frequencies of polymorphic GSTM1, GSTT1, and cytochrome P450 CYP1A1 in Mexicans. Hum Biol 79:299–312

    Article  PubMed  Google Scholar 

  30. Gaspar PA, Hutz MH, Salzano FM, Hill K, Hurtado AM, Petzl-Erler ML, Tsuneto LT, Weimer TA (2002) Polymorphisms of CYP1a1, CYP2e1, GSTM1, GSTT1, and TP53 genes in Amerindians. Am J Phys Anthropol 119:249–256

    Article  PubMed  Google Scholar 

  31. Al-Dayel F, Al-Rasheed M, Ibrahim M, Bu R, Bavi P, Abubaker J, Al-Jomah N, Mohamed GH, Moorji A, Uddin S, Siraj AK, Al-Kuraya K (2008) Polymorphisms of drug-metabolizing enzymes CYP1A1, GSTT and GSTP contribute to the development of diffuse large B-cell lymphoma risk in the Saudi Arabian population. Leuk Lymphoma 49:122–129

    Article  CAS  PubMed  Google Scholar 

  32. Dandara C, Sayi J, Masimirembwa CM, Magimba A, Kaaya S, De Sommers K, Snyman JR, Hasler JA (2002) Genetic polymorphism of cytochrome P450 1A1 (Cyp1A1) and glutathione transferases (M1, T1 and P1) among Africans. Clin Chem Lab Med 40:952–957

    Article  CAS  PubMed  Google Scholar 

  33. Yalin S, Hatungil R, Tamer L, Ates NA, Dogruer N, Yildirim H, Karakas S, Atik U (2007) Glutathione S-transferase gene polymorphisms in Turkish patients with diabetes mellitus. Cell Biochem Funct 25:509–513

    Article  CAS  PubMed  Google Scholar 

  34. Millikan R, Pittman G, Tse CK, Savitz DA, Newman B, Bell D (2000) Glutathione S-transferases M1, T1, and P1 and breast cancer. Cancer Epidemiol Biomarkers Prev 9:567–573

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by a grant by University “Tor Vergata” (RSA 2008) allotted to M.F. Authors thank Prof D. Frezza, of the same University, who provided DNA samples from Cameroon. Human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards as laid down by law.

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Correspondence to Maria Fuciarelli.

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Piacentini, S., Polimanti, R., Porreca, F. et al. GSTT1 and GSTM1 gene polymorphisms in European and African populations. Mol Biol Rep 38, 1225–1230 (2011). https://doi.org/10.1007/s11033-010-0221-0

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  • DOI: https://doi.org/10.1007/s11033-010-0221-0

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