Advertisement

Molecular and Cellular Biochemistry

, Volume 389, Issue 1–2, pp 79–84 | Cite as

Polymorphisms in glutathione S-transferase are risk factors for perioperative acute myocardial infarction after cardiac surgery: a preliminary study

  • Viktória Kovacs
  • Balazs Gasz
  • Borbala Balatonyi
  • Luca Jaromi
  • Peter Kisfali
  • Balazs Borsiczky
  • Gabor Jancso
  • Nandor Marczin
  • Sandor Szabados
  • Bela Melegh
  • Alotti Nasri
  • Elisabeth Roth
Article

Abstract

In the present study we explored glutathione S-transferase (GST) polymorphisms in selected patients who experienced accelerated myocardial injury following open heart surgery and compared these to a control group of patients without postoperative complications. 758 Patients were enrolled from which 132 patients were selected to genotype analysis according to exclusion criteria. Patients were divided into the following groups: Group I: control patients (n = 78) without and Group II.: study patients (n = 54) with evidence of perioperative myocardial infarction. Genotyping for GSTP1 A (Ile105Ile/Ala113Ala), B (Ile105Val/Ala113Ala) and C (Ile105Val/Ala113Val) alleles was performed by using real-time-PCR. The heterozygous AC allele was nearly three times elevated (18.5 vs. 7.7 %) in the patients who suffered postoperative myocardial infarction compared to controls. Contrary, we found allele frequency of 14.1 % for homozygous BB allele in the control group whereas no such allele combination was present in the study group. These preliminary results may suggest the protective role for the B and C alleles during myocardial oxidative stress whereas the A allele may represent predisposing risk for cellular injury in patients undergoing cardiac surgery.

Keywords

Cardiac surgery Perioperative acute myocardial infarction Gene polymorphism Glutathione S-transferase P1 

Notes

Acknowledgments

This work was supported by the Hungarian Science Research Fund OTKA K78434 and the TÁMOP 4.2.2./B-10/1-2010-0029. The study was approved by TUKEB (3727.316-3255/2010).

References

  1. 1.
    Yau JM, Alexander JH, Hafley G et al (2008) Impact of perioperative myocardial infarction on angiographic and clinical outcomes following coronary artery bypass grafting (from project of ex-vivo vein graft engineering via transfection (PREVENT) IV). Am J Cardiol 102:546–551PubMedCrossRefGoogle Scholar
  2. 2.
    Mangano DT (1997) Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials. The multicenter study of perioperative ischemia (McSPI) research group. JAMA 277:325–332PubMedCrossRefGoogle Scholar
  3. 3.
    Nalysnyk L, Fahrbach K, Reynolds MW (2003) Adverse events in coronary artery bypass graft (CABG) trials: a systematic review and analysis. Heart 89:767–772PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Thielmann M, Massoudy P, Schmermund A et al (2005) Diagnostic discrimination between graft-related and non-graft-related perioperative myocardial infarction with cardiac troponin I after coronary artery bypass surgery. Eur Heart J 26:2440–2447PubMedCrossRefGoogle Scholar
  5. 5.
    Mohammed AA, Agnihotri AK, van Kimmenade RR et al (2009) Prospective, comprehensive assessment of cardiac troponin T testing after coronary artery bypass graft surgery. Circulation 120:843–850PubMedCrossRefGoogle Scholar
  6. 6.
    Alexander JH, Hafley G, Harrington RA et al (2005) Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial. JAMA 294:2446–2454PubMedCrossRefGoogle Scholar
  7. 7.
    Podgoreanu MV, White WD, Morris RW et al (2006) Perioperative genetics and safety outcomes study (PEGASUS) Investigative team. Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery. Circulation 114:275–281CrossRefGoogle Scholar
  8. 8.
    Liu Kuang-Yu, Muehlschlegel Jochen D, Perry Tjörvi E et al (2010) Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg 139:483–488PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Roth E, Hejjel L (2003) Oxygen free radicals in heart disease. In: Pugsley MK (ed) Cardiac Drug Development Guide. Humana Press, New jersy, pp 47–66CrossRefGoogle Scholar
  10. 10.
    Elahi MM, Khan JS, Matata BM (2006) Deleterious effects of cardiopulmonary bypass in coronary artery surgery and scientific interpretation of off-pump’s logic. Acute Card Care 8:196–209PubMedCrossRefGoogle Scholar
  11. 11.
    Butler J, Rocker GM, Westaby S (1993) Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 55:552–559PubMedCrossRefGoogle Scholar
  12. 12.
    Hall RI, Smith MS, Rocker G (1997) The systemic inflammatory response to cardiopulmonary bypass: pathophysiological, therapeutic, and pharmacological considerations. Anesth Analg 85:766–782PubMedGoogle Scholar
  13. 13.
    Wan S, LeClerc JL, Vincent JL (1997) Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest 112:676–692PubMedCrossRefGoogle Scholar
  14. 14.
    Sharma R, Gupta S, Singhal SS, Ahmad H, Haque A, Awasthi YC (1991) Independent segregation of glutathione S-transferase and fatty acid ethyl ester synthase from pancreas and other human tissues. Biochem J 275:507–513PubMedCentralPubMedGoogle Scholar
  15. 15.
    Ali-Osman F, Akande O, Antoun G et al (1997) Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants: evidence for differential catalytic activity of the encoded proteins. J Biol Chem 272:10004–10012PubMedCrossRefGoogle Scholar
  16. 16.
    Volzke H, Engel J, Kleine V et al (2002) Angiotensin I-converting enzyme insertion/deletion polymorphism and cardiac mortality and morbidity after coronary artery bypass graft surgery. Chest 122:31–36PubMedCrossRefGoogle Scholar
  17. 17.
    Fox Amanda A, Collard Charles D, Shernan Stanton K et al (2009) Natriuretic peptide system gene variants are associated with ventricular dysfunction after coronary artery bypass grafting. Anesthesiology 110:738–747PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Emiroglu Ozan, Durdu Serkan, Egin Yonca et al (2011) Thrombotic gene polymorphisms and postoperative outcome after coronary artery bypass graft surgery. J Cardiothorac Surg 6:120PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Tekeli A, Isbir S, Ergen A et al (2008) APE1 and XRCC3 polymorphisms and myocardial infarction. In Vivo 22:477–479PubMedGoogle Scholar
  20. 20.
    Lobato RL, White WD, Mathew JP et al (2011) Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses. Circulation 124:S143–S148PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Eifert S, Rasch A, Beiras-Fernandez A et al (2009) Gene polymorphisms in APOE, NOS3, and LIPC genes may be risk factors for cardiac adverse events after primary CABG. J Cardiothorac Surg 4:46PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Frey UH, Kottenberg E, Kamler M et al (2011) Genetic interactions in the b-adrenoceptor/G-protein signal transduction pathway and survival after coronary artery bypass grafting: a pilot study. Br J Anaesth 107:869–878PubMedCrossRefGoogle Scholar
  23. 23.
    Stępień E, Krawczyk S, Kapelak B et al (2011) Effect of the E-selectin gene polymorphism (S149R) on platelet activation and adverse events after coronary artery surgery. Arch Med Res 42:375–381PubMedCrossRefGoogle Scholar
  24. 24.
    Muehlschlegel JD, Liu KY, Perry TE et al (2010) Chromosome 9p21 variant predicts mortality after coronary artery bypass graft surgery. Circulation 122:S60–S65PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Virani SS, Brautbar A, Lee VV et al (2012) Chromosome 9p21 single nucleotide polymorphisms are not associated with recurrent myocardial infarction in patients with established coronary artery disease. Circ J 76:950–956PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Isbir S, Ergen A, Yilmaz H et al (2008) Effect of Ala16Val genetic polymorphism of MnSOD on antioxidant capacity and inflammatory response in open heart surgery. In Vivo 22:147–151PubMedGoogle Scholar
  27. 27.
    Kornblit B, Munthe-Fog L, Madsen HO et al (2008) Association of HMGB1 polymorphisms with outcome in patients with systemic inflammatory response syndrome. Crit Care 12:R83PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Wypasek E, Stepien E, Kot M et al (2012) Fibrinogen beta-chain -C148T polymorphism is associated with increased fibrinogen, C-reactive protein, and interleukin-6 in patients undergoing coronary artery bypass grafting. Inflammation 35:429–435PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Perry TE, Muehlschlegel JD, Liu KY et al (2009) C-Reactive protein gene variants are associated with postoperative C-reactive protein levels after coronary artery bypass surgery. BMC Med Genet 10:38PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Hayes JD, McLellan LI (1999) Glutathione and glutathione-dependent enzymes represent a co- ordinately regulated defence against oxidative stress. Free Radical Res 31:273–300CrossRefGoogle Scholar
  31. 31.
    Suvakov S, Damjanovic T, Stefanovic A et al (2013) 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 28:202–212PubMedCrossRefGoogle Scholar
  32. 32.
    McIlwain CC, Townsend DM, Tew KD (2006) Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene 25:1639–1648PubMedCrossRefGoogle Scholar
  33. 33.
    Ruscoe JE, Rosario LA, Wang T et al (2001) Pharmacologic or genetic manipulation of glutathione S-transferase P1-1 (GSTpi) influences cell proliferaton pathways. J Pharmacol Exp Ther 298:339–345PubMedGoogle Scholar
  34. 34.
    Christie JD, Aplenc R, DeAdrade J et al (2005) Donor glutathione S-transferase genotype is assotiated with primary graft dysfunction following lung transplantation. J Heart Lung Transplant 24:S80CrossRefGoogle Scholar
  35. 35.
    Hadjiliadis D, Lingaraju R, Mendez J et al (2007) Donor glutathione S-transferase (GST) mu null genotype in lung transplant recipients is assotiated with increased incidence of bronchiolitis obliterans (BOS) independent of acute rejection. J Heart Lung Transplant 26:S108CrossRefGoogle Scholar
  36. 36.
    Cora T, Tokac M, Acar H et al (2013) Glutathione S-transferase M1 and T1 genotypes and myocardial infarction. Mol Biol Rep 40:3263–3267PubMedCrossRefGoogle Scholar
  37. 37.
    Wilson MH, Grant PJ, Kain K et al (2003) Association between the risk of coronary artery disease in South Asians and a deletion polymorphism in glutathione S-transferase M1. Biomarkers 8:43–50PubMedCrossRefGoogle Scholar
  38. 38.
    Wilson MH, Grant PJ, Hardie LJ et al (2000) Glutathione S-transferase M1 null genotype is associated with a decreased risk of myocardial infarction. FASEB J 14:791–796PubMedGoogle Scholar
  39. 39.
    Nomani H, Mozafari H, Ghobadloo SM et al (2011) The association between GSTT1, M1, and P1 polymorphisms with coronary artery disease in Western Iran. Mol Cell Biochem 354:181–187PubMedCrossRefGoogle Scholar
  40. 40.
    Moscow JA, Fairchild CR, Madden MJ et al (1989) Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res 49:1422–1428PubMedGoogle Scholar
  41. 41.
    Allan JM, Wild CP, Rollinson S et al (2001) Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia. Proc Natl Acad Sci USA 98:11592–11597PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Tuna G, Kulaksiz Erkmen G, Dalmizrak O et al (2010) Inhibition characteristics of hypericin on rat small intestine glutathione-S-transferases. Chem Biol Interact: 18859–18865Google Scholar
  43. 43.
    Henderson CJ, Wolf CR, Kitteringham N et al (2000) Increased resistance to acetaminophen hepatotoxicity in mice lacking glutathione S-transferase Pi. Proc Natl Acad Sci USA 97:12741–12745PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Viktória Kovacs
    • 1
  • Balazs Gasz
    • 2
  • Borbala Balatonyi
    • 1
  • Luca Jaromi
    • 3
  • Peter Kisfali
    • 3
  • Balazs Borsiczky
    • 1
  • Gabor Jancso
    • 1
  • Nandor Marczin
    • 4
  • Sandor Szabados
    • 5
  • Bela Melegh
    • 3
  • Alotti Nasri
    • 2
  • Elisabeth Roth
    • 1
  1. 1.Department of Surgical Research and Techniques, Medical FacultyUniversity of PécsPecsHungary
  2. 2.Department of Cardiac SurgeryZala County HospitalZalaegerszegHungary
  3. 3.Department of Medical GeneticsUniversity of PécsPecsHungary
  4. 4.Faculty of Medicine, Imperial College of LondonLondonUK
  5. 5.Heart Institute, Medical Faculty, University of PécsPecsHungary

Personalised recommendations