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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Lawes CM, Vander Hoorn S, Rodgers A. Global burden of blood-pressure-related disease, 2001. Lancet. 2008;371:1513–8.
Touyz RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance? Hypertension. 2004;44:248–52.
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.
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.
Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005;45:51–88.
Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology. 2000;61:154–66.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.
DerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials. 2007;28:105–14.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.
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.
Hirschhorn JN, Lohmueller K, Byrne E. A comprehensive review of genetic association studies. Genet Med. 2002;4:45–61.
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.
Conflict of interest
The authors declare that they have no conflict of interest.