Skip to main content

Advertisement

Log in

Effects of myeloperoxidase −463 G/A gene polymorphism and plasma levels on coronary artery disease

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Myeloperoxidase is a lysosomal enzyme of polymorphonuclear leucocytes that contributes to inflamatory responses. In previous studies it was shown that MPO was synthesized in atherosclerotic lesions responsible of lipoprotein oxidations. We aimed to determine the MPO −463 G/A gene polymorphism distribution in Turkish population and evaluate the effects of it on myeloperoxidase levels. There were 100 myocardial infarct patients and 100 healthy control subjects in our study. MPO polymorphism was studied by using PCR-RFLP technique and MPO levels were measured by ELISA. It was shown that MPO levels were increasing in patients after myocardial infarct event but there were no effect of MPO −463 G/A polymorphism on MPO levels. It was also found that serum total cholesterol and LDL-cholesterol levels and smoking was contributing factors in increments of MPO enzymes. We observed that MPO levels were increased in CAD but there were no effect of MPO −463 G/A polymorphism on MPO levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Klebanoff SJ, Waltersdorph AM, Rosen H (1984) Antimicrobial activity of myeloperoxidase. Methods Enzymol 105:399–403

    Article  CAS  PubMed  Google Scholar 

  2. Zhang R, Shen Z, Nauseef WM, Hazen SL (2002) Defects in leukocytemediated initiation of lipid peroxidation in plasma as studied in myeloperoxidase-deficient subjects: systematic identification of multiple endogenous diffusible substrates for myeloperoxidase in plasma. Blood 99:1802–1810

    CAS  PubMed  Google Scholar 

  3. Zhang R, Brennan ML, Shen Z, MacPherson JC, Schmitt D, Molenda CE, Hazen SL (2002) Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation. J Biol Chem 277:46116–46122

    Article  CAS  PubMed  Google Scholar 

  4. Sugiyama S, Okada Y, Sukhova GK, Virmani R, Heinecke JW, Libby P (2001) Macrophage myeloperoxidase regulation by macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. Am J Pathol 158:879–891

    CAS  PubMed  Google Scholar 

  5. Zhang R, Brennan ML, Fu X, Aviles RJ, Pearce GL, Penn MS, Topol EJ, Sprecher DL, Hazen SL (2001) Association between myeloperoxidase levels and risk of coronary artery disease. JAMA 286:2136–2142

    Article  CAS  PubMed  Google Scholar 

  6. Klebanoff SJ (1980) Oxygen metabolism and the toxic properties of phagocytes. Ann Intern Med 93:480–489

    CAS  PubMed  Google Scholar 

  7. Abu-Soud HM, Hazen SL (2000) Nitric oxide is a physiological substrate for mammalian peroxidases. J Biol Chem 275:37524–37532

    Article  CAS  PubMed  Google Scholar 

  8. Eiserich JP, Baldus S, Brennan ML, Ma W, Zhang C, Tousson A, Castro L, Lusis AJ, Nauseef WM, White CR, Freeman BA (2002) Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science 296:2391–2394

    Article  CAS  PubMed  Google Scholar 

  9. Fu X, Kassim SY, Parks WC, Heinecke JW (2001) Hypochlorous acid oxygenates the cysteine switch domain of pro-matrilysin (MMP-7): a mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase. J Biol Chem 276:41279–41287

    Article  CAS  PubMed  Google Scholar 

  10. Podrez EA, Schmidt D, Hoff HF, Hazen SL (1999) Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro. J Clin Invest 103:1547–1560

    Article  CAS  PubMed  Google Scholar 

  11. Podrez EA, Poliakov E, Shen Z, Zhang R, Deng Y, Sun M, Finton PJ, Shan L, Febbraio M, Hajjar DP, Silverstein RL, Hoff HF, Salomon RG, Hazen SL (2002) A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions. J Biol Chem 277:38517–38523

    Article  CAS  PubMed  Google Scholar 

  12. Schmitt D, Shen Z, Zhang R, Colles SM, Wu W, Salomon RG, Chen Y, Chisolm GM, Hazen SL (1999) Leukocytes utilize myeloperoxidase-generated nitrating intermediates as physiological catalysts for the generation of biologically active oxidized lipids and sterols in serum. Biochem 38:16904–16915

    Article  CAS  Google Scholar 

  13. Shabani F, McNeil J, Tippett L (1998) The oxidative inactivation of tissue inhibitor of metalloproteinase-1 (TIMP-1) by hypochlorous acid (HOCl) is suppressed by anti-rheumatic drugs. Free Radic Res 28:115–123

    Article  CAS  PubMed  Google Scholar 

  14. Piedrafita FJ, Molander RB, Vansant G, Orlova EA, Pfahl M, Reynolds WF (1996) An Alu element in the myeloperoxidase promoter contains a composite SP1-thyroid hormone-retinoic acid response element. J Biol Chem 271:14412–14420

    Article  CAS  PubMed  Google Scholar 

  15. Hoy A, Tregouet D, Leininger-Muller B, Poirier O, Maurice M, Sass C, Siest G, Tiret L, Visvikis S (2001) Serum myeloperoxidase concentration in a healthy population: biological variations, familial resemblance and new genetic polymorphisms. Eur J Hum Genet 9:780–786

    Article  CAS  PubMed  Google Scholar 

  16. Nikpoor B, Turecki G, Fournier C, Theroux P, Rouleau GA (2001) A functional myeloperoxidase polymorphic variant is associated with coronary artery disease in French-Canadians. Am Heart J 142:336–339

    Article  CAS  PubMed  Google Scholar 

  17. Pecoits-Filho R, Stenvinkel P, Marchlewska A, Heimburger O, Bárány P, Hoff CM, Holmes CJ, Suliman M, Lindholm B, Schalling M, Nordfors L (2003) A functional variant of the myeloperoxidase gene is associated with cardiovascular disease in end-stage renal disease patients. Kidney Int 84:S172–S176

    Article  CAS  Google Scholar 

  18. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of low density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 18:499–508

    CAS  PubMed  Google Scholar 

  19. Miller SA, Dykes DD, Polesky HS (1988) Simples salting-out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res 16(3):1215

    Article  CAS  PubMed  Google Scholar 

  20. Roncaglioni M, Santoro L, D’Avanzo B, Negri E, Nobili A, Ledda A, Pietropaolo F, Franzosi MG, La Vecchia C, Feruglio GA, Maseri A (1992) On behalf of GISSI-EFRIM Investigators. The role of family history in patients with myocardial infarction: an Italian case-control study. GISSI-EFRIM Investigators. Circulation 85:2065–2072

    CAS  PubMed  Google Scholar 

  21. Cambon F (1999) Genetic prediction of myocardial infarction. Blood Coagul Fibrinol 10:S23–S24

    Article  Google Scholar 

  22. Karaali ZE, Sozen S, Yurdum M, Cacina C, Toptas B, Gok O, Agachan B (2010) Effect of genetic variants of chemokine receptors on the development of myocardial infarction in Turkish population. Mol Biol Rep Feb 25. [Epub ahead of print]

  23. Zhong C, Luzhan Z, Genshan M, Jiahong W, Xiaoli Z, Qi Q (2010) Monocyte chemoattractant protein-1-2518 G/A polymorphism, plasma levels, and premature stable coronary artery disease. Mol Biol Rep 37(1):7–12

    Article  PubMed  Google Scholar 

  24. Chen LL, Zhu TB, Yin H, Huang J, Wang LS, Cao KJ, Yang ZJ (2009) Inhibition of MAPK signaling by eNOS gene transfer improves ventricular remodeling after myocardial infarction through reduction of inflammation. Mol Biol Rep Nov 12. [Epub ahead of print]

  25. Pasalić D, Marinković N, Grsković B, Ferencak G, Bernat R, Stavljenić-Rukavina A (2009) C-reactive protein gene polymorphisms affect plasma CRP and homocysteine concentrations in subjects with and without angiographically confirmed coronary artery disease. Mol Biol Rep 36(4):775–780

    Article  PubMed  Google Scholar 

  26. Tang JJ, Wang MW, Jia EZ, Yan JJ, Wang QM, Zhu J, Yang ZJ, Lu X, Wang LS (2010) 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 37(1):405–410

    Article  CAS  PubMed  Google Scholar 

  27. Carr AC, McCall MR, Frei B (2001) Oxidation of LDL by myeloperoxidase and reactive nitrogen species. Arterioscler Thromb Vasc Biol 20:1716–1723

    Google Scholar 

  28. Asselbergs FW, Reynolds WF, Cohen-Tervaert JW, Jessurun GAJ (2004) Myeloperoxidase polymorphism related to cardiovascular events in coronary artery disease. Am J Med 116:429–430

    Article  CAS  PubMed  Google Scholar 

  29. Stefanescua A, Braun S, Ndrepepa G, Kopara T, Pavaci H, Mehilli J, Schömig A, Kastrati A (2008) Prognostic value of plasma myeloperoxidase concentration in patients with stable coronary artery disease. Am Heart J 155:356–360

    Article  Google Scholar 

  30. Ndrepepa G, Braun S, Mehilli J, von Beckerath N, Schömig A, Kastrati A (2008) Myeloperoxidase level in patients with stable coronary artery disease and acute coronary syndromes. Eur J Clin Invest 38(2):90–96

    Article  CAS  PubMed  Google Scholar 

  31. Duzguncınar O, Yavuz B, Hazirolan T (2008) Plasma myeloperoxidase is related to the severity of coronary artery disease. Acta Cardiol 63(2):147–152

    Article  PubMed  Google Scholar 

  32. Lau D, Baldus S (2006) Myeloperoxidase and its contributory role in inflammatory vascular disease. Pharmacol Ther 111:16–26

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by TUBITAK as project no: 107S289.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Arzu Ergen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ergen, A., İsbir, S., Timirci, Ö. et al. Effects of myeloperoxidase −463 G/A gene polymorphism and plasma levels on coronary artery disease. Mol Biol Rep 38, 887–891 (2011). https://doi.org/10.1007/s11033-010-0181-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-0181-4

Keywords

Navigation