Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Glutathione S-Transferase M1 and T1 polymorphisms and hypertension risk: an updated meta-analysis

Journal of Human Hypertension volume 33, pages 454–465 (2019)Cite this article

Subjects

Abstract

Recently, Glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and their interaction with hypertension risk have been focused on. However, the results of previous studies have been inconsistent. Hence, the present meta-analysis was performed to explore the association. Twenty-two case-control studies met the inclusion criteria for GSTM1 (including 3577 hypertension cases and 3784 controls), twenty-two for GSTT1 (including 3741 cases and 4444 controls), and nine for their combined effects (including 1073 cases and 781 controls). Pooled analyses on the association between GSTM1 present/null polymorphism and hypertension risk were observed to be insignificant in overall and subgroup analyses. The individual who carries the GSTT1 null-genotype had a statistically significant overall population (OR = 1.28, 95% CI: 1.03, 1.60), Indians (OR = 2.45, 95% CI: 1.08, 5.59), and hospital-based controls (OR = 1.53, 95% CI: 1.21, 1.94). For the GSTM1-GSTT1 interaction, we found that the GSTM1/GSTT1 double-null-genotype was significantly associated with hypertension risks (double-null vs. double-present: OR = 2.68, 95% CI: 1.06, 6.81). To summarize, this meta-analysis indicates that Indians with the GSTT1 null-genotype has a raised hypertension risks; the GSTM1 null/GSTT1 null-genotype is association with raised hypertension risks, while the GSTM1 null-genotype is not associated with hypertension risks. In addition, I2 > 75% cannot be eliminated for GSTM1 in Indians or Asians, hence, it will be very important to explore the GSTM1 null-genotype and hypertension susceptibility in Indians and Asians for a large new sample, on population-based control study.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Lawes CM, Vander Hoorn S, Rodgers A. Global burden of blood-pressure-related disease, 2001. Lancet. 2008;371:1513–8.

    Article  PubMed  Google Scholar 

  2. Touyz RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance? Hypertension. 2004;44:248–52.

    Article  CAS  PubMed  Google Scholar 

  3. Johnson RJ, Rodriguez-Iturbe B, Kang DH, Feig DI, Herrera-Acosta J. A unifying pathway for essential hypertension. Am J Hypertens. 2005;18:431–40.

    Article  PubMed  Google Scholar 

  4. Hayes JD, Pulford DJ. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol. 1995;30:445–600.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology. 2000;61:154–66.

    Article  CAS  PubMed  Google Scholar 

  7. Pearson WR, Vorachek WR, Xu SJ, Berger R, Hart I, Vannais D, et al. Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. Am J Hum Genet. 1993;53:220–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Yalin S, Hatungil R, Tamer L, Aras Ates N, Dogruer N, Yildirim H, et al. Glutathione S-transferase gene polymorphisms in Turkish patients with diabetes mellitus. Cell Biochem Funct. 2007;25:509–13.

    Article  CAS  PubMed  Google Scholar 

  9. Keladaa SN, Stapletona PL, Farina FM, Bammlera TK, Eaton DL, Smith-Wellera T, et al. Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson’s Disease. Neurosci Lett. 2003;337:5–8.

    Article  Google Scholar 

  10. Park JH, El-Sohemy A, Cornelis MC, Kim HA, Kim SY, Bae SC. Glutathione S-transferase M1, T1,and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. Rheumatol Int. 2004;24:157–63.

    Article  PubMed  Google Scholar 

  11. Singh M, Shah PP, Singh AP, Ruwali M, Mathur N, Pant MC, et al. Association of genetic polymorphisms in glutathione S-transferases and susceptibility to head and neck cancer. Mutat Res. 2008;638:184–94.

    Article  CAS  PubMed  Google Scholar 

  12. Lewis SJ, Cherry NM, Niven RMCL, Barber PV, Povey AC. GSTM1, GSTT1 and GSTP1 polymorphisms and lung cancer risk. Cancer Lett. 2002;180:165–71.

    Article  CAS  PubMed  Google Scholar 

  13. Hussain K, Salah N, Hussain S, Hussain S. Investigate the role of glutathione S Transferase (GST) polymorphism in development of hypertension in UAE Population. Iran Red Crescent Med J. 2012;14:479–82.

    PubMed  PubMed Central  Google Scholar 

  14. Lee BK, Lee SJ, Joo JS, Cho KS, Kim NS, Kim NS, et al. Association of Glutathione S-Transferase genes (GSTM1 and GSTT1) polymorphisms with hypertension in lead-exposed workers. Mol Cell Toxicol. 2012;8:203–8.

    Article  CAS  Google Scholar 

  15. Miranda-Vilela AL, Akimoto AK, Alves PC, Ferreira LB, Lordelo GS, Melo JG, et al. Evidence for an association between haptoglobin and MnSOD (Val9Ala) gene polymorphisms in essential hypertension based on a Brazilian case-control study. Genet Mol Res. 2010;9:2166–75.

    Article  CAS  PubMed  Google Scholar 

  16. Polimanti R, Piacentini S, Lazzarin N, Re MA, Manfellotto D, Fuciarelli M. Glutathione S-transferase variants as risk factor for essential hypertension in Italian patients. Mol Cell Biochem. 2011;357:227–33.

    Article  CAS  PubMed  Google Scholar 

  17. Bessa SS, Ali EM, Hamdy SM. The role of glutathione S- transferase M1 and T1 gene polymorphisms and oxidative stress-related parameters in Egyptian patients with essential hypertension. Eur J Intern Med. 2009;20:625–30.

    Article  CAS  PubMed  Google Scholar 

  18. Borah PK, Shankarishan P, Mahanta J. Glutathione S-transferase. M1 and T1 gene polymorphisms and risk of hypertension in tea garden workers of North-East India. Genet Test Mol Biomark. 2011;15:771–6.

    Article  CAS  Google Scholar 

  19. Capoluongo E, Onder G, Concolino P, Russo A, Santonocito C, Bernabei R, et al. GSTM1-null polymorphism as possible risk marker for hypertension: results from the aging and longevity study in the Sirente Geographic Area (ilSIRENTE study). Clin Chim Acta. 2009;399:92–96.

    Article  CAS  PubMed  Google Scholar 

  20. Cruz-Gonzalez I, Corral E, Sanchez-Ledesma M, Sanchez-Rodriguez A, Martin-Luengo C, Gonzalez-Sarmiento R. An association between resistant hypertension and the null GSTM1 genotype. J Hum Hypertens. 2009;23:556–8.

    Article  CAS  PubMed  Google Scholar 

  21. Jiang X, Castelao JE, Yuan JM, Groshen S, Stern MC, Conti DV, et al. Hypertension, diuretics and anti-hypertensives in relation to bladder cancer. Carcinogenesis. 2010;31:1964–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Marinho C, Alho I, Arduíno D, Falcão LM, Brás-Nogueira J, Bicho M. GSTM1/T1 and MTHFR polymorphisms as risk factors for hypertension. Biochem Biophys Res Commun. 2007;353:344–50.

    Article  CAS  PubMed  Google Scholar 

  23. Oniki K, Hori M, Takata K, Yokoyama T, Mihara S, Marubayashi T, et al. Association between glutathione Stransferase A1, M1 and T1 polymorphisms and hypertension. Pharm Genom. 2008;18:275–7.

    Article  CAS  Google Scholar 

  24. Turkanoglu A, Can Demirdogen B, Demirkaya S, Bek S, Adali O. Association analysis of GSTT1, GSTM1 genotype polymorphisms and serum total GST activity with ischemic stroke risk. Neurol Sci. 2010;31:727–34.

    Article  PubMed  Google Scholar 

  25. Wang R, Wang Y, Wang J, Yang K. Association of glutathione S-transferase T1 and M1 gene polymorphisms with ischemic stroke risk in the Chinese Han population. Neural Regen Res. 2012;7:1420–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Han JH, Lee HJ, Choi HJ, Yun KE, Kang MH. Lymphocyte DNA damage and plasma antioxidant status in Korean subclinical hypertensive patients by glutathione S-transferase polymorphism. Nutr Res Pract. 2017;11:214–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Petrovič D, Peterlin B. GSTM1-null and GSTT1-null-genotypes are associated with essential arterial hypertension in patients with type 2 diabetes. Clin Biochem. 2014;47:574–7.

    Article  PubMed  Google Scholar 

  28. Levinsson A, Olin AC, Modig L, Dahgam S, Björck L, Rosengren A, et al. Interaction effects of long-term air pollution exposure and variants in the GSTP1, GSTT1 and GSTCD genes on risk of acute myocardial infarction and hypertension: a case-control study. PLoS ONE. 2014;9:e99043.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Abbas S, Raza ST, Chandra A, Rizvi S, Ahmed F, Eba A, et al. Association of ACE, FABP2 and GST genes polymorphism with essential hypertension risk among a North Indian population. Ann Hum Biol. 2015;42:461–9.

    Article  PubMed  Google Scholar 

  30. Ellithy HN, Yousri S, Shahin GH. Relation between glutathione S-transferase genes (GSTM1, GSTT1, and GSTP1) polymorphisms and clinical manifestations of sickle cell disease in Egyptian patients. Hematology. 2015;20:598–606.

    Article  CAS  PubMed  Google Scholar 

  31. Rizvi S, Raza ST, Siddiqi Z, Abbas S, Mahdi F. Association of angiotensin-converting enzyme and glutathione S-Transferase genepolymorphisms with body mass index among hypertensive North Indians. Sultan Qaboos Univ Med J. 2015;15:e477–85.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Eslami S, Sahebkar A. Glutathione-S-transferase M1 and T1 null-genotypes are associated with hypertension risk: a systematic review and meta-analysis of 12 studies. Curr Hypertens Rep. 2014;16:432.

    Article  PubMed  Google Scholar 

  33. Ge B, Song Y, Zhang Y, Liu X, Wen Y, Guo X. Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null polymorphisms and the risk of hypertension: a meta-analysis. PLoS ONE. 2015;10:e0118897.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.

    CAS  PubMed  Google Scholar 

  35. DerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials. 2007;28:105–14.

    Article  PubMed  Google Scholar 

  36. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  37. Yang Y, Kao MT, Chang CC, Chung SY, Chen CM, Tsai JJ, et al. Glutathione S-transferase T1 deletion is a risk factor for developing end-stage renal disease in diabetic patients. Int J Mol Med. 2004;14:855–9.

    CAS  PubMed  Google Scholar 

  38. Hirschhorn JN, Lohmueller K, Byrne E. A comprehensive review of genetic association studies. Genet Med. 2002;4:45–61.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No 81441014 to BL), the Shanxi Province Natural Science Foundation (No 2012011040-3 to X-LW, 2013011049-4 to S-LR), the Research Project of Shanxi Provincial Health and Family Planning Commission (201602026 to S-LR, 201602028 to X-LW), the High School 131 Leading Talent Project of Shanxi Province to S-LR, and the National Undergraduate Innovation and Entrepreneurship Training Programs (201610117001 to S-LR). The funders had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China

    Shu-Ling Rong, Yu-Chuan Wang & Bao Li

  2. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. China

    Xue-Dong Zhou & Ze-Kun Wang

  3. Department of Pediatrics, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China

    Xiao-Lin Wang

  4. Department of Neurology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China

    Cun-Shui Xue

Authors
  1. Shu-Ling Rong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xue-Dong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ze-Kun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Lin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yu-Chuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cun-Shui Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xiao-Lin Wang or Bao Li.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rong, SL., Zhou, XD., Wang, ZK. et al. Glutathione S-Transferase M1 and T1 polymorphisms and hypertension risk: an updated meta-analysis. J Hum Hypertens 33, 454–465 (2019). https://doi.org/10.1038/s41371-018-0133-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41371-018-0133-3

This article is cited by

Search

Advanced search

Quick links