Advertisement

Analysis of GSTM1, GSTT1, and CYP1A1 in Idiopathic Male Infertility

Abstract

Enzymes belonging to the glutathione-S-transferase (GST) and cytochrome P450 (CYP) families are involved in a 2-stage detoxification process of a wide range of environmental toxins and carcinogens. In order to investigate whether there is a genetic association of the biotransformation enzymes and idiopathic male fertility, we studied GSTT1, GSTM1, and CYP1A1*2A polymorphisms in 150 infertile men and 200 healthy men as controls from Northern Iran. Genotyping of the GSTT1 and GSTM1 genes were performed using the multiplex polymerase chain reaction (PCR). However, the CYP1A1 polymorphism was determined using PCR-restriction fragment length polymorphism (RFLP). The GSTM1 and GSTT1 null genotypes were present at frequencies of 0.61 and 0.34 in infertile cases, whereas in controls the frequencies were 0.33 and 0.17, respectively. Double-null genotype was found to be elevated among infertile men (odds ratio [OR] = 3.75, 95% confidence interval [CI] = 2.42-6.45; P < .0001). The frequency of TT, TC, and CC genotypes of CYP1A1 polymorphism in the controls were 42.5%, 45.5%, and 12%, respectively, while those in the infertile men were 38.7%, 48%, and 13.3%. The CYP1A1*2A did not display any association with male infertility. We observed an association between male infertility and the GSTM1 and GSTT1 null deletion, but not with the CYP1A1 polymorphism in North Iranian men with idiopathic infertility.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 510

This is the net price. Taxes to be calculated in checkout.

References

  1. 1.

    Pasqualotto FF, Pasqualotto EB, Sobreiro BP, Hallak J, Medeiros F, Lucon AM. Clinical diagnosis in men undergoing infertility investigation in a university hospital. Urol Int. 2006;76(2):122–125.

  2. 2.

    Baker MA, Aitken RJ. Proteomic insights into spermatozoa: critiques, comments and concerns. Expert Rev Proteomics. 2009; 6(6):691–705.

  3. 3.

    Finotti AC, Costa E, Silva RC, Bordin BM, Silva CT, Moura KK. Glutathione S-transferase M1 and T1 polymorphism in men with idiopathic infertility. Genet Mol Res. 2009;8(3):1093–1098.

  4. 4.

    Safarinejad MR, Shafiei N, Safarinejad S. The association of glutathione-S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) with idiopathic male infertility. J Hum Genet. 2010; 55(9):565–570.

  5. 5.

    Chen SS, Chang LS, Chen HW, Wei YH. Polymorphisms of glutathione S-transferase M1 and male infertility in Taiwanese patients with varicocele. Hum Reprod. 2002;17(3):718–725.

  6. 6.

    Aydos SE, Taspinar M, Sunguroglu A, Aydos K. Association of CYP1A1 and glutathione S-transferase polymorphisms with male factor infertility. Fertil Steril. 2009;92(2):541–547.

  7. 7..

    Eaton DL, Bammler TK. Glutathione S-transferases. In: Levy RH, Thummel KE, Trager WF, Hansten PD, Eichelbaum M, eds. Metabolic Drug Interactions. Philadelphia, PA: Lippincott, Williams & Wilkins; 2000:175–189.

  8. 8..

    Listowsky, I. High capacity binding by glutathione S-transferases and glucocorticoid resistance. In: Tew KD, Pickett CB, Mantle TJ, Mannervik B, Hayes JD, eds. Structure and Function of Glutathione Transferases. Boca Raton, FL: CRC Press; 1993:199–209.

  9. 9.

    Seidegård J, Vorachek WR, Pero RW, Pearson WR. Hereditary differences in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion. Proc Natl Acad Sci U S A. 1988;85(19):7293–7297.

  10. 10.

    Neri M, Taioli E, Filiberti R, et al. Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: a comparison of Finnish and Italian populations. Int J Hyg Environ Health. 2006;209(4):393–398.

  11. 11.

    Sprenger R, Schlagenhaufer R, Kerb R, et al. Characterization of the glutathione S-transferase GSTT1 deletion: discrimination of all genotypes by polymerase chain reaction indicates a trimodular genotype-phenotype correlation. Pharmacogenetics. 2000;10(6): 557–565.

  12. 12.

    Parl FF. Glutathione S-transferase genotypes and cancer risk. Cancer Lett. 2005;221(2):123–129.

  13. 13.

    Hayashi S, Watanabe J, Nakachi K, Kawajiri K. Genetic linkage of lung cancer-associated MspI polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene. J Biochem. 1991;110(3):407–411.

  14. 14.

    Cosma G, Crofts F, Taioli E, Toniolo P, Garte S. Relationship between genotype and function of the human CYP1A1 gene. J Toxicol Environ Health. 1993;40(2–3):309–316.

  15. 15..

    World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction; 1999.

  16. 16.

    Arand M, Mühlbauer R, Hengstler J, et al. A multiplex polymerase chain reaction protocol for the simultaneous analysis of the glutathione S-transferase GSTM1 and GSTT1 polymorphisms. Anal Biochem. 1996;236(1):184–186.

  17. 17.

    Suryanarayana V, Deenadayal M, Singh L. Association of CYP1A1 gene polymorphism with recurrent pregnancy loss in the South Indian population. Hum Reprod. 2004;19(11):2648–2652.

  18. 18.

    Su MT, Chen CH, Kuo PH, et al. Polymorphisms of estrogen-related genes jointly confer susceptibility to human spermatogenic defect. Fertil Steril. 2010;93(1):141–149.

  19. 19.

    Beckett GJ, Hayes JD. Glutathione S-transferases: biomedical applications. Adv Clin Chem. 1993;30:281–380.

  20. 20.

    Makker K, Agarwal A, Sharma R. Oxidative stress & male infertility. Indian J Med Res. 2009;129(1):357–367.

  21. 21.

    Aydemir B, Onaran I, Kiziler AR, Alici B, Akyolcu MC. The influence of oxidative damage on viscosity of seminal fluid in infertile men. J Androl. 2008;29(1):41–46.

  22. 22.

    Tirumala Vani G, Mukesh N, Siva Prasad B, et al. Role of glutathione S-transferase Mu-1 (GSTM1) polymorphism in oli-gospermic infertile males. Andrologia. 2010;42(4):213–217.

  23. 23.

    Lu N, Wu B, Xia Y, et al. Polymorphisms in CYP1A1 gene are associated with male infertility in a Chinese population. Int J Androl. 2008;31(5):527–533.

Download references

Author information

Correspondence to Zivar Salehi MD, PhD.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Salehi, Z., Gholizadeh, L., Vaziri, H. et al. Analysis of GSTM1, GSTT1, and CYP1A1 in Idiopathic Male Infertility. Reprod. Sci. 19, 81–85 (2012). https://doi.org/10.1177/1933719111413302

Download citation

Keywords

  • GSTM1
  • GSTT1
  • CYP1A1
  • idiopathic male infertility