Skip to main content
SpringerLink
Log in

Combined Effect of GSTT1 and GSTM1 Polymorphisms on Human Male Infertility in North Indian Population

  • Original Articles
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Genes of different pathways regulate spermatogenesis, and complexity of spermatogenic process indicates that polymorphisms or mutations in these genes could cause male infertility. Detoxification pathway is involved in the regulation of spermatogenesis by reducing oxidative stress and contributes to the maintenance of global methylation in concert with other pathways. Glutathione S-transferases (GSTs) belong to the family of phase II antioxidant enzymes involved in the cellular detoxification of various physiological substances. Glutathione S-transferases act as an antioxidant and protect spermatozoa from oxidative stress. Increase in the levels of reactive oxygen species (ROS) along with reduced activity of GSTs may result in sperm membrane damage and DNA fragmentation. A case–control study was done to elucidate the role of deletion polymorphism of GSTT1 and GSTM1 genes from GSTs family on idiopathic human male infertility. The study comprises 2 groups: 113 nonobstructive azoospermia patients and 91 healthy fertile controls. Genomic DNA was analyzed by polymerase chain reaction for GSTT1 and GSTM1 genes. The study showed statistically significant protective association of GSTT1 null genotype with human male infertility (odds ratio [OR]: 0.3, 95% confidence interval [CI] 0.143-0.9966, P = .048) but not with GSTM1 null genotype (OR: 0.66, 95% CI 0.3653-1.2234, P = .19). Also, combination of null genotypes of GSTM1 and GSTT1 confers protective effect (OR: 0.28, CI 0.0801-0.948; P = .04). Probably, individuals bearing GSTM1 and GSTT1 (−/−) genotypes may have protective effect by gene–gene interaction mechanism. In summary, our study underscores the significance of combined effect of GSTT1 and GSTM1 null genotypes in modulating the risk of male infertility.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Matzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nat Med. 2008;14(11): 1197–1213.

    Article  CAS  Google Scholar 

  2. Matzuk MM, Lamb DJ. Genetic dissection of mammalian fertility pathways. Nat cell Biol. 2002; (suppl 4):S41–S49.

  3. McLachlan RI, Bryan MK. State of the art for genetic testing of infertile men. J Clin Endocrinol Metab. 2010;95(3):1013–1024.

    Article  CAS  Google Scholar 

  4. Nachtigall RD. International disparities in access to infertility services. Fertil Steril. 2006;85(4):871–875.

    Article  Google Scholar 

  5. Merzenich H, Zeeb H, Blettner M. Decreasing sperm quality: a global problem? BMC Public Health. 2010;10:24.

    Google Scholar 

  6. Lewis SEM, Aitken RJ. DNA damage to spermatozoa has impacts on fertilization and pregnancy. Cell Tissue Res. 2005;322(1): 33–41.

    Article  CAS  Google Scholar 

  7. Shamsi MB, Venkatesh S, Kumar R, et al. Antioxidant levels in blood and seminal plasma and their impact on sperm parameters in infertile men. Indian J Biochem Biophys. 2010; 47(1):38–43.

    CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  Google Scholar 

  9. Rubes J, Selevan SG, Sram RJ, Evenson DP, Perreault SD. GSTM1 genotype influences the susceptibility of men to sperm DNA damage associated with exposure to air pollution. Mutat Res. 2007;625(1–2):20–28.

    Article  CAS  Google Scholar 

  10. Babu KA, Rao KL, Kanakavalli M K, Suryanarayana VV, Deenadayal M, Singh L. CYP1A1, GSTM1 and GSTT1 genetic polymorphism is associated with susceptibility to polycystic ovaries in South Indian women. Reprod Biomed Online. 2004;9(2): 194–200.

    Article  CAS  Google Scholar 

  11. Ding Y, Chen ZF, Lin RY, et al. Relationship between endometriosis and glutathione S-transferase M1, T1 genes of the Uygurs and Hans in Xinjiang [in Chinese]. Zhonghua Fu Chan Ke Za Zhi. 2004;39(2):101–104.

    PubMed  Google Scholar 

  12. Sergentanis TN, Economopoulos KP. GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2009;121(1):195–202.

    Article  Google Scholar 

  13. Gopalakrishnan B, Shaha C. Inhibition of sperm glutathione S-transferase leads to functional impairment due to membrane damage. FEBS Lett 1998;422(3):296–300.

    Article  CAS  Google Scholar 

  14. Strange RC, Spiteri MA, Ramachandran S, Fryer AA. Glutathione-Stransferase family of enzymes. Mutat Res. 2001; 482(1–2):21–26.

    Article  CAS  Google Scholar 

  15. Pemble S, Schroeder KR, Spencer SR, et al. Human glutathione S-transferase Theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J. 1994;300(pt 1): 271–276.

    Article  CAS  Google Scholar 

  16. Castellon EA. Influence of age, hormones and germ cells on glutathione S-transferase activity in cultured Sertoli cells. Int J Androl. 1999;22(1):49–55.

    Article  CAS  Google Scholar 

  17. Zamudio NM, Chong S, O’Bryan MK. Epigenetic regulation in male germ cells. Reproduction. 2008;136(2):131–146.

    Article  CAS  Google Scholar 

  18. Zhong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK. Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 1993;14(9): 1821–1824.

    Article  CAS  Google Scholar 

  19. Katoh T, Nagata N, Kuroda Y, et al. Glutathione S-transferase M1 (GSTM1), and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. Carcinogenesis. 1996;17(9):1855–1859.

    Article  CAS  Google Scholar 

  20. Erdfelder E, Faul F, Buchner A. G*POWER: A general power analysis program. Behav Res Meth Instrum Comput. 1996;28: 1–11.

    Article  Google Scholar 

  21. Mann CL, Davies MB, Boggild MD, et al. Glutathione S-transferase polymorphisms in MS: their relationship to disability. Neurology 2000;54(3):552–557.

    Article  CAS  Google Scholar 

  22. Pasqualotto FF, Sharma RK, Nelson DR, Thomas AJ, Agarwal A. Relationship between oxidative stress, semen characteristics and clinical diagnosis in men undergoing infertility investigation. Fertil Steril. 2000;73(3):459–464.

    Article  CAS  Google Scholar 

  23. Agarwal A, Said TM. Oxidative stress, DNA damage and apoptosis in male infertility: a clinical approach. BJU Int. 2005;95(4): 503–507.

    Article  CAS  Google Scholar 

  24. Polonikov AV, Yarosh SL, Kokhtenko EV, Starodubova NI, Pakhomov SP, Orlova VS. The functional genotype of glutathione S-transferase T1 gene is strongly associated with increased risk of idiopathic infertility in Russian men. Fertil Steril. 2010;94(3): 1144–1147.

    Article  CAS  Google Scholar 

  25. Wu QF, Xing JP, Tang KF, et al. Genetic polymorphism of glutathione S-transferase T1 gene and susceptibility to idiopathic azoospermia or oligospermia in northwestern China. Asian J Androl 2008;10(2):266–270.

    Article  CAS  Google Scholar 

  26. 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.

    Article  CAS  Google Scholar 

  27. Dordevic V, Nikolic A, Ljujic M, et al. Combined effect of GSTM1 gene deletion, GSTT1 gene deletion and MTHFR C677T mutation in male infertility. Arch Biol Sci. 2010;62(3):525–530.

    Article  Google Scholar 

  28. Dhillon VS, Shahid M, Husain SA. Associations of MTHFR DNMT3b 4977 bp deletion in mtDNA and GSTM1 deletion, and aberrant CpG island hypermethylation of GSTM1 in nonobstructive infertility in Indian men. Mol Hum Reprod. 2007; 13(4):213–222.

    Article  CAS  Google Scholar 

  29. Vani GT, Mukesh N, Siva Prasad B, et al. Role of glutathione S-transferase Mu-1 (GSTM1) polymorphism in oligospermic infertile males. Andrologia. 2009;42(4):213–217.

    Article  Google Scholar 

  30. Khazamipour N, Noruzinia M, Fatehmanesh P, Keyhanee M, Pujol P. MTHFR promoter hypermethylation in testicular biopsies of patients with non-obstructive azoospermia: the role of epigenetics in male infertility. Hum Reprod. 2009;24(9):2361–2364.

    Article  CAS  Google Scholar 

  31. Singh K, Singh SK, Sah R, Singh I, Raman R. Mutation C677T in the methylenetetrahydrofolate reductase gene is associated with male infertility in an Indian population. Int J Androl. 2005; 28(2):115–119.

    Article  CAS  Google Scholar 

  32. Paracchini V, Garte S, Taioli E. MTHFR, C677T polymorphism, GSTM1 deletion and male infertility: a possible suggestion of a gene-gene interaction? Biomarkers. 2006;11(1):53–60.

    Article  CAS  Google Scholar 

  33. Economopoulos KP, Sergentanis TN, Choussein S., Glutathione-S-transferase gene (GSTM1, GSTT1 and GSTP1) and idiopathic male infertility: novel perspectives versus facts. J Hum Genet. 2010;55(9):557–558.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    Deepika Jaiswal MSc & Kiran Singh PhD

  2. Sah Speciality Clinic, Ravindrapuri Colony, Durgakund, Varanasi, Uttar Pradesh, India

    Ravindra Sah MS

  3. Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Neeraj K. Agrawal DM

  4. Department of Urology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    U. S. Dwivedi MCh & Sameer Trivedi MCh

Authors
  1. Deepika Jaiswal MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ravindra Sah MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neeraj K. Agrawal DM
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. U. S. Dwivedi MCh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sameer Trivedi MCh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kiran Singh PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kiran Singh PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jaiswal, D., Sah, R., Agrawal, N.K. et al. Combined Effect of GSTT1 and GSTM1 Polymorphisms on Human Male Infertility in North Indian Population. Reprod. Sci. 19, 312–316 (2012). https://doi.org/10.1177/1933719111424451

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719111424451

Keywords

Search

Navigation