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

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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.

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  1. 1.

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

  2. 2.

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

  3. 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.

  4. 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.

  5. 5.

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

  6. 6.

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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. 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.

  29. 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.

  30. 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.

  31. 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.

  32. 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.

  33. 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.

  34. 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.

  35. 35.

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

  36. 36.

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

  37. 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.

  38. 38.

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

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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.

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Correspondence to Xiao-Lin Wang or Bao Li.

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