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  • 1 Department of Vascular Surgery Semmelweis University, Városmajor u. 68, H-1122, Budapest, Hungary
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Abstract

The development of atherosclerosis is a multifactorial process. The purpose of the study was to examine three genetic polymorphisms playing a role in the metabolic processes underlying the disease. We compared the data of 348 atherosclerotic non-diabetic patients with 260 atherosclerotic diabetic patients and 384 healthy controls. We analyzed the prevalence of myocardial infarction and stroke in three different groups of patients carrying different polymorphisms. It was proved that if the mutant TT eNOS Glu298ASP variant is present, a significantly higher number of myocardial infarctions can be observed than in patients carrying heterozygote GT or normal GG genotype. We proved that in the case of MTHFR 677CT heterozygote variants, the occurrence of myocardial infarction is significantly higher and the difference is also significant in case of the 677TT homozygote variant. It was verified that among patients with the mutant TNF-α AA genotype the occurrence of cardiovascular events was significantly higher. Screening the genetically high risk groups on the long run should be considered as an early detection opportunity that may give better chances for prevention and treatment. Understanding the inflammatory mechanisms of the atherosclerosis may give new therapeutical targets to pharmacologists.

  • 1. L. Szollár 2005 Kórélettan Az atherosclerosis Szollár L, Semmelweis Kiadó Budapest 304 328.

  • 2. Meskó L. Szollár 1999 Az arteriosclerosis kórélettana. Meskó C. Farsang Z. Pécsvárady Belgyógyászati angiologia Medintel Könyvkiadó Budapest 55 67.

    • Search Google Scholar
    • Export Citation
  • 3. N. Hosszúfalusi 2000 A hyperglycaemia szerepe a diabetes mellitus késői szövődményeinek kialakulásában LAM 10 1 40 48.

  • 4. G. Jermendi 2001 Diabetes mellitus és az artérias érbetegségek Hippocrates 3 5 319 314.

  • 5. Nieszner P. Bárdos Baranyi I. Préda 2005 A diabetes mellitus cardiovascularis szövődményei és diagnózisuk LAM 15 10 722 729.

  • 6. A. Lusis 2000 Atherosclerosis Nature 407 14 233 241.

  • 7. Szalai Cs : Atherosclerosis. Genetikai alapok. Jegyzet 118 (2009).

  • 8. J. Willerson P. Ridker 2004 Inflammation as a cardiovascular risk factor Circulation 109 2 10.

  • 9. G. Blanke P. Ridker 2001 Inflammatory mechanisms in atherosclerosis: from laboratory evidence to clinical application Ital Heart J 2 11 796 800.

    • Search Google Scholar
    • Export Citation
  • 10. R. Corti R. Hutter J.J. Badimon V. Fuster 2004 Evolving concepts in the triad of atherosclerosis, inflammation and thrombosis J Thromb Thrombolysis 17 1 35 44.

    • Search Google Scholar
    • Export Citation
  • 11. P. Libby P.M. Ridker A. Maseri 2002 Inflammation and atherosclerosis Circulation 105 1135 1143.

  • 12. R. Ross 1999 Atherosclerosis-an inflammatory disease N Engl J Med 340 115 126.

  • 13. J. Davignon P. Ganz 2004 Role of endothelial dysfunction in atherosclerosis Circulation 109 27 3.

  • 14. T.J. DeGraba 2004 Immunogenetic susceptibility of atherosclerotic stroke: implications on current and future treatment of vascular inflammation Stroke 35 2712 2719.

    • Search Google Scholar
    • Export Citation
  • 15. N. Giese M. Marijianowski O. McCook A. Hancock V. Ramakrishnan L. Fretto C. Chen A. Kelly J. Koziol J. Wilcox S. Hanson 1999 The role of alpha and beta platelet-derived growth factor in the vascular response to injury in nonhuman primates Atheroscler Thromb Vasc Biol 19 900 909.

    • Search Google Scholar
    • Export Citation
  • 16. B.R. Jaeger C.A. Labarrrere 2003 Fibrinogen und atherothrombose: vulnerable plaque oder vulnerabler patient? Herz 28 530 538.

  • 17. P. Ridker N. Rifai M. Pfeffer F. Sacks S. Lepage E. Braunwald 2000 Elevation of tumor necrosis factor-alfa, and increased risk of recurrent coronary events after myocardial infarction Circulation 101 2149 2153.

    • Search Google Scholar
    • Export Citation
  • 18. M. Gardner J. Palmer C. Manrique G. Lestra D.W. Gardner J.R. Sower 2009 Utility of aspirin therapy in patients with the cardiometabolic syndrome and diabetes J Cardiometab Syndr 4 2 96 101.

    • Search Google Scholar
    • Export Citation
  • 19. T. Geisler D.L. Bhatt 2004 The role of inflammation in atherosclerosis: current and future strategies of medical treatment Med Sci Monit 10 12 308 316.

    • Search Google Scholar
    • Export Citation
  • 20. A. Halliday A. Mansfield J. Marro C. Peto R. Peto J. Potter D. Thomas 2004 MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group: prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial Lancet 363 1491 1502.

    • Search Google Scholar
    • Export Citation
  • 21. M.G. Colombo U. Paradossi M.G. Andreassi N. Botto S. Manfredi S. Masetti A. Biagini A. Clerico 2003 Endothelial nitric oxide synthase gene polymorphisms and risk of coronary artery disease Clin Chem 49 389 395.

    • Search Google Scholar
    • Export Citation
  • 22. A. Hingorani C. Liang J. Fatibene S. Monteith A. Parsons S. Haydock R. Hopper N. Stephens 1999 a common variant of the endothelial nitric oxid synthase (Glu298-Asp) is a major risk factor for coronary artery disease in the UK Circulation 100 1515 1520.

    • Search Google Scholar
    • Export Citation
  • 23. G.P. Rossi M. Cesari M. Zanchetta S. Colonna G. Maiolino L. Pedon M. Cavallin P. Maiolino A.C. Pessina 2003 The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study J Am Coll Cardiol 41 930 937.

    • Search Google Scholar
    • Export Citation
  • 24. Z. Yang X. Ming 2006 Recent advances in understanding endothelial dysfunction in atherosclerosis Clin Med Res 4 1 53 65.

  • 25. A.S. Marroni I.F. Metzger D.C. Souza-Costa S. Nagassaki V.C. Sandrim R.X. Correa F. Rios-Santos J.E. Tanus-Santos 2005 Consistent interethnic differences in the distribution of clinically relevant endothelial nitric oxide synthase genetic polymorphisms Nitric Oxide 12 177 182.

    • Search Google Scholar
    • Export Citation
  • 26. J. Selhub P.F. Jacques A.G. Bostom R.B. D Agostino P.W. Wilson A.J. Belanger D.H. O Leary P.A. Wolf E.J. Schaefer I.H. Rosenberg 1995 Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis N Engl J Med 332 286 291.

    • Search Google Scholar
    • Export Citation
  • 27. I. Bova J. Chapman C. Sylantiev A.D. Korczyn N.M. Bornstein 1999 The A677V methylenetetrahydrofolate reductase gene polymorphism and carotid atherosclerosis Stroke 30 2180 2182.

    • Search Google Scholar
    • Export Citation
  • 28. A. Mazza D. Giugliano C. Motti C. Cortese F. Andreotti G. Marra A. Nulli 2000 Glycemia, MTHFR genotype and low homocysteine in uncomplicated type 2 diabetic patients Atherosclerosis 149 223 224.

    • Search Google Scholar
    • Export Citation
  • 29. M.S. Elkind J. Cheng B. Boden-Albala T. Rundek J. Thomas H. Chen L.E. Rabbani R.L. Sacco 2002 Tumor necrosis factor receptor levels are associated with carotid atherosclerosis Stroke 33 31 38.

    • Search Google Scholar
    • Export Citation
  • 30. B.L. Goodwin L.C. Pendleton M.M. Levy L.P. Solomonson D.C. Eichler 2007 Tumor necrosis factor-α reduces argininosuccinate synthase expression and nitric oxide production in aortic endothelial cells Am J Physiol Heart Circ Physiol 293 1115 1121.

    • Search Google Scholar
    • Export Citation
  • 31. P.S. Monraats N.M.M. Pires A. Schepers W. Agema L. Boesten M. Vries A. Zwinderman M. de Maat P. Doevendans R. Winter R. Tio J. Waltenberger L. Hart R. Frants P. Quax B. Vlijmen L. Havekes A. Laarse E. Wall W. Jukema 2005 Tumor necrosis factor-α plays an important role in restenosis development FASEB J 19 1998 2004.

    • Search Google Scholar
    • Export Citation
  • 32. J.M. Fernandez-Real C. Gutierrez W. Ricart R. Casamitjana M. Fernandez-Castaner J. Vendrell C. Richart J. Soler 1997 The TNF-alpha gene Nco I polymorphism influences the relationship among insulin resistance, percent body fat, and increased serum leptin levels Diabetes 46 9 2096 2098.

    • Search Google Scholar
    • Export Citation
  • 33. Szél B. Merkely K. Hüttl J. Gál B. Nemes A. Komócsi 2010 Statement of ethical publishing and scientific authorship Int Med Appl Sci 2 101 102.

    • Search Google Scholar
    • Export Citation
  • 34. G.V. Szabó A. Kunstár G. Acsády 2009 Methylentetrahydrofolate reductase and nitric oxide synthase polymorphism in patients with atherosclerosis and diabetes Pathol Oncol Res 15 631 637.

    • Search Google Scholar
    • Export Citation
  • 35. G.V. Szabó G. Acsády 2011 Tumornecrosis-factor-α 308 GA Polymorphism in atherosclerotic patients Pathol Oncol Res 17 853 857.

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