DOI QR코드

DOI QR Code

Lymphocyte DNA damage and plasma antioxidant status in Korean subclinical hypertensive patients by glutathione S-transferase polymorphism

  • Han, Jeong-Hwa (Nutrition Safety Policy Division, Food Nutrition and Dietary Safety Bureau, Ministry of Food and Drug Safety) ;
  • Lee, Hye-Jin (Department of Food Science and Nutrition, Daedeok Valley Campus, Hannam University) ;
  • Choi, Hee Jeong (Department of Family Medicine, Eulji University School of Medicine) ;
  • Yun, Kyung Eun (Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Kang, Myung-Hee (Department of Food Science and Nutrition, Daedeok Valley Campus, Hannam University)
  • Received : 2016.12.09
  • Accepted : 2017.02.01
  • Published : 2017.06.01

Abstract

BACKGROUND/OBJECTIVES: Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of xenobiotics by conjugating substances with glutathione. The aim of this study is to assess the antioxidative status and the degree of DNA damage in the subclinical hypertensive patients in Korea using glutathione S-transferase polymorphisms. SUBJECTS/METHODS: We examined whether DNA damage and antioxidative status show a difference between GSTM1 or GSTT1 genotype in 227 newly diagnosed, untreated (systolic blood pressure $(BP){\geq}130mmHg$ or diastolic $BP{\geq}85mmHg$) subclinical hypertensive patients and 130 normotensive subjects (systolic BP < 120 mmHg and diastolic BP < 80 mmHg). From the blood of the subjects, the degree of the DNA damage in lymphocyte, the activities of erythrocyte superoxide dismutase, the catalase, and the glutathione peroxidase, the level of glutathione, plasma total radical-trapping antioxidant potential (TRAP), anti-oxidative vitamins, as well as plasma lipid profiles and conjugated diene (CD) were analyzed. RESULTS: Of the 227 subjects studied, 68.3% were GSTM1 null genotype and 66.5% were GSTT1 null genotype. GSTM1 null genotype had an increased risk of hypertension (OR: 2.104, CI: 1.38-3.35), but no significant association in GSTT1 null genotype (OR 0.982, CI: 0.62-1.55). No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and plasma TRAP, CD, lipid profiles, and GSH levels were observed between GSTM1 or GSTT1 genotype. Plasma levels of ${\alpha}-tocopherol$ increased significantly in GSTT1 wild genotype (P < 0.05); however, plasma level of ${\beta}-carotene$ increased significantly in GSTT1 null genotype (P < 0.01). DNA damage assessed by the Comet assay was significantly higher in GSTM1 null genotype than wild genotype (P < 0.05). CONCLUSIONS: These results confirm the association between GSTM1 null genotype and risk of hypertension as they suggest that GSTM1 null genotype leads to an increased oxidative stress compared with wild genotype.

Keywords

References

  1. Dominiczak AF, Negrin DC, Clark JS, Brosnan MJ, McBride MW, Alexander MY. Genes and hypertension: from gene mapping in experimental models to vascular gene transfer strategies. Hypertension 2000;35:164-72. https://doi.org/10.1161/01.HYP.35.1.164
  2. Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Ann Intern Med 2003;139:761-76. https://doi.org/10.7326/0003-4819-139-9-200311040-00011
  3. Ahmad A, Singhal U, Hossain MM, Islam N, Rizvi I. The role of the endogenous antioxidant enzymes and malondialdehyde in essential hypertension. J Clin Diagn Res 2013;7:987-90.
  4. Gur M, Yildiz A, Demirbag R, Yilmaz R, Kocyigit A, Celik H, Aksoy N. Relationship between left ventricle geometric patterns and lymphocyte DNA damage in patients with untreated essential hypertension. Clin Biochem 2007;40:454-9. https://doi.org/10.1016/j.clinbiochem.2006.10.024
  5. Han JH, Lee HJ, Choi HJ, Yun KE, Kang MH. Association between oxidative stress and blood pressure in Korean subclinical hypertensive patients. Korean J Nutr 2013;46:126-36. https://doi.org/10.4163/kjn.2013.46.2.126
  6. Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 2000;61:154-66. https://doi.org/10.1159/000028396
  7. Rebbeck TR. Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 1997;6:733-43.
  8. Han JH, Lee HJ, Kim TS, Kang MH. The effect of glutathione S-transferase M1 and T1 polymorphisms on blood pressure, blood glucose, and lipid profiles following the supplementation of kale (Brassica oleracea acephala) juice in South Korean subclinical hypertensive patients. Nutr Res Pract 2015;9:49-56. https://doi.org/10.4162/nrp.2015.9.1.49
  9. Cho MR, Han JH, Lee HJ, Park YK, Kang MH. Purple grape juice supplementation in smokers and antioxidant status according to different types of GST polymorphisms. J Clin Biochem Nutr 2015;56: 49-56. https://doi.org/10.3164/jcbn.14-1
  10. Pavanello S, Clonfero E. Biological indicators of genotoxic risk and metabolic polymorphisms. Mutat Res 2000;463:285-308. https://doi.org/10.1016/S1383-5742(00)00051-X
  11. Binkova B, Lewtas J, Miskova I, Rossner P, Cerna M, Mrackova G, Peterkova K, Mumford J, Meyer S, Sram R. Biomarker studies in northern Bohemia. Environ Health Perspect 1996;104 Suppl 3:591-7. https://doi.org/10.1289/ehp.96104s3591
  12. Jeon GI, Park EJ. Effect of glutathione s-transferase polymorphisms on the antioxidant system. J Korean Soc Food Sci Nutr 2007;36:708-19. https://doi.org/10.3746/jkfn.2007.36.6.708
  13. Capoluongo E, Onder G, Concolino P, Russo A, Santonocito C, Bernabei R, Zuppi C, Ameglio F, Landi F. 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;399:92-6. https://doi.org/10.1016/j.cca.2008.09.017
  14. Saadat M, Dadbine-Pour A. Influence of polymorphism of glutathione S-transferase M1 on systolic blood pressure of normotensive individuals. Biochem Biophys Res Commun 2005;326:449-54. https://doi.org/10.1016/j.bbrc.2004.11.050
  15. Oniki K, Hori M, Takata K, Yokoyama T, Mihara S, Marubayashi T, Nakagawa K. Association between glutathione S-transferase A1, M1 and T1 polymorphisms and hypertension. Pharmacogenet Genomics 2008;18:275-7. https://doi.org/10.1097/FPC.0b013e3282f56176
  16. Marinho C, Alho I, Arduino D, Falcao LM, Bras-Nogueira J, Bicho M. GST M1/T1 and MTHFR polymorphisms as risk factors for hypertension. Biochem Biophys Res Commun 2007;353:344-50. https://doi.org/10.1016/j.bbrc.2006.12.019
  17. Kim H, Kim WJ, Lee HL, Lee MS, Kim CH, Kim RS, Nam HM. A case-control study on the effects of the genetic polymorphisms of N-acetyltransferase 2 and glutathione S-transferase mu and theta on the risk of bladder cancer. Korean J Prev Med 1998;31:275-84.
  18. Kim SJ, Kim MG, Kim KS, Song JS, Yim SV, Chung JH. Impact of glutathione S-transferase M1 and T1 gene polymorphisms on the smoking-related coronary artery disease. J Korean Med Sci 2008;23: 365-72. https://doi.org/10.3346/jkms.2008.23.3.365
  19. Bell DA, Taylor JA, Paulson DF, Robertson CN, Mohler JL, Lucier GW. Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst 1993;85:1159-64. https://doi.org/10.1093/jnci/85.14.1159
  20. Lee HJ, Park YK, Kang MH. The effect of carrot juice, ${\beta}$-carotene supplementation on lymphocyte DNA damage, erythrocyte antioxidant enzymes and plasma lipid profiles in Korean smoker. Nutr Res Pract 2011;5:540-7. https://doi.org/10.4162/nrp.2011.5.6.540
  21. Park EJ, Kim JS, Jeon EJ, Kim HY, Park YK, Kang MH. The effects of purple grape juice supplementation on improvement of antioxidant status and lymphocyte DNA damage in Korean smokers. Korean J Nutr 2004;37:281-90.
  22. Lee BK, Lee SJ, Joo JS, Cho KS, Kim NS, Kim HJ. Association of Glutathione S-transferase genes (GSTM1 and GSTT1) polymorphisms with hypertension in lead-exposed workers. Mol Cell Toxicol 2012;8:203-8. https://doi.org/10.1007/s13273-012-0025-5
  23. Jo HR, Lee HJ, Kang MH. Antioxidative status, DNA damage and lipid profiles in Korean young adults by glutathione S-transferase polymorphisms. Korean J Nutr 2011;44:16-28. https://doi.org/10.4163/kjn.2011.44.1.16
  24. Dusinska M, Ficek A, Horska A, Raslova K, Petrovska H, Vallova B, Drlickova M, Wood SG, Stupakova A, Gasparovic J, Bobek P, Nagyova A, Kovacikova Z, Blazicek P, Liegebel U, Collins AR. Glutathione S-transferase polymorphisms influence the level of oxidative DNA damage and antioxidant protection in humans. Mutat Res 2001;482:47-55. https://doi.org/10.1016/S0027-5107(01)00209-3
  25. Block G, Shaikh N, Jensen CD, Volberg V, Holland N. Serum vitamin C and other biomarkers differ by genotype of phase 2 enzyme genes GSTM1 and GSTT1. Am J Clin Nutr 2011;94:929-37. https://doi.org/10.3945/ajcn.111.011460
  26. Tang JJ, Wang MW, Jia EZ, Yan JJ, Wang QM, Zhu J, Yang ZJ, Lu X, Wang LS. The common variant in the GSTM1 and GSTT1 genes is related to markers of oxidative stress and inflammation in patients with coronary artery disease: a case-only study. Mol Biol Rep 2010;37:405-10. https://doi.org/10.1007/s11033-009-9877-8
  27. Reszka E, Wasowicz W, Gromadzinska J. Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case-control study. Genes Nutr 2007;2:287-94. https://doi.org/10.1007/s12263-007-0057-y
  28. Tang K, Xue W, Xing Y, Xu S, Wu Q, Liu R, Wang X, Xing J. Genetic polymorphisms of glutathione S-transferase M1, T1, and P1, and the assessment of oxidative damage in infertile men with varicoceles from northwestern China. J Androl 2012;33:257-63. https://doi.org/10.2164/jandrol.110.012468
  29. Lin YS, Hung SC, Wei YH, Tarng DC. GST M1 polymorphism associates with DNA oxidative damage and mortality among hemodialysis patients. J Am Soc Nephrol 2009;20:405-15. https://doi.org/10.1681/ASN.2008020227
  30. Papas AM. Determinants of antioxidant status in humans. Lipids 1996;31 Suppl:S77-82. https://doi.org/10.1007/BF02637055
  31. Hayek T, Stephens JW, Hubbart CS, Acharya J, Caslake MJ, Hawe E, Miller GJ, Hurel SJ, Humphries SE. A common variant in the glutathione S transferase gene is associated with elevated markers of inflammation and lipid peroxidation in subjects with diabetes mellitus. Atherosclerosis 2006;184:404-12. https://doi.org/10.1016/j.atherosclerosis.2005.05.017
  32. Rahman SH, Nanny C, Ibrahim K, O'Reilly D, Larvin M, Kingsnorth AJ, McMahon MJ. Genetic polymorphisms of GSTT1, GSTM1, GSTP1, MnSOD, and catalase in nonhereditary chronic pancreatitis: evidence of xenobiotic stress and impaired antioxidant capacity. Dig Dis Sci 2005;50:1376-83. https://doi.org/10.1007/s10620-005-2790-7
  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. https://doi.org/10.1016/j.ejim.2009.06.003
  34. Kang MH, Yun JS. The effects of exercise and other relating factors on the activity of erythrocyte antioxidant enzymes and plasma TRAP levels in male college students. Korean J Nutr 2002;35:30-6.
  35. Suvakov S, Damjanovic T, Stefanovic A, Pekmezovic T, Savic-Radojevic A, Pljesa-Ercegovac M, Matic M, Djukic T, Coric V, Jakovljevic J, Ivanisevic J, Pljesa S, Jelic-Ivanovic Z, Mimic-Oka J, Dimkovic N, Simic T. Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients. Nephrol Dial Transplant 2013;28:202-12. https://doi.org/10.1093/ndt/gfs369
  36. Silva DG, Belini Junior E, Torres LS, Ricci Junior O, Lobo CC, Bonini-Domingos CR, de Almeida EA. Relationship between oxidative stress, glutathione S-transferase polymorphisms and hydroxyurea treatment in sickle cell anemia. Blood Cells Mol Dis 2011;47:23-8. https://doi.org/10.1016/j.bcmd.2011.03.004
  37. 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. https://doi.org/10.1038/jhh.2009.19
  38. Silva BR, Pernomian L, Bendhack LM. Contribution of oxidative stress to endothelial dysfunction in hypertension. Front Physiol 2012;3:441.
  39. Chandra S, Romero MJ, Shatanawi A, Alkilany AM, Caldwell RB, Caldwell RW. Oxidative species increase arginase activity in endothelial cells through the RhoA/Rho kinase pathway. Br J Pharmacol 2012;165:506-19. https://doi.org/10.1111/j.1476-5381.2011.01584.x

Cited by

  1. Glutathione S-Transferase M1 and T1 polymorphisms and hypertension risk: an updated meta-analysis pp.1476-5527, 2018, https://doi.org/10.1038/s41371-018-0133-3
  2. A systematic review and meta-analyses of the relationship between glutathione S-transferase gene polymorphisms and renal cell carcinoma susceptibility vol.19, pp.1, 2018, https://doi.org/10.1186/s12881-018-0620-y
  3. Genetic polymorphisms associated with reactive oxygen species and blood pressure regulation pp.1473-1150, 2019, https://doi.org/10.1038/s41397-019-0082-4
  4. DNA damage protection: an excellent application of bioactive compounds vol.6, pp.1, 2019, https://doi.org/10.1186/s40643-019-0237-9