Clinical and Prognostic Value of Endothelial NO-Synthetase Gene Polymorphism in Patients with Acute Coronary Syndromes
DOI:
https://doi.org/10.22141/2224-0586.3.58.2014.83250Keywords:
gene polymorphism, endothelial NO-synthetase, endothelial dysfunction, pulse ware velocity, acute coronary syndrome, thrombolytic therapyAbstract
Nitric oxide (NO) is produced by endothelial nitric oxide synthetase (eNOS) and plays important role in normal vascular homeostasis. In the eNOS gene various polymorphisms have been identified. The -786T>C polymorphism in the gene promoter has been demonstrated to modulate the eNOS gene expression and so the synthesis of NO.
325 patients with ACS and 83 healthy controls were investigated. The eNOS polymorphism has been analyzed by polymerase chain reaction and restriction fragment length polymorphism. In Ukrainians the C/C genotype in the eNOS gene promoter was more common than in Japanese and less common than in west Europeans, north Americans and Australians. A significant difference in genotype distribution was observed between patients and controls. Pathological C/C genotype was significantly more often determined in ACS patients, especially in men younger than 55 years old.
-786CC genotype was associated with increase in arterial stiffness and lower flow-mediated brachial artery dilatation. -786TT variant of the eNOS gene promoter in investigated patients was associated with better efficacy of reperfusion therapy. Patients with -786TT genotype had fewer complications during the period of hospitalization.
References
Гватуа Н.А., Солоненко И.Н., Шкляр Л.В. Особенности формирования зоны некроза при крупноочаговом и мелкоочаговом инфаркте миокарда // Кардиология. — 1988. — № 11. — С. 112-114.
Досенко В.Є., Загорій В.Ю., Мойбенко О.О., Пархоменко О.М. Патофізіологічні аспекти генетичного поліморфізму ендотеліальної NO-синтази // Фізіол. журн. — 2002. — Т. 48, № 6. — С. 86-102.
Мойбенко О.О., Павлюченко В.Б., Даценко В.В. та ін. Дослідження ролі ендотелійзалежних факторів у реалізації кардіогенних рефлексів за нормальних та патологічних умов // Фізіол. журн. — 2000. — Т. 46, № 2. — С. 19-32.
Мoйбенко О.О., Сагач В.Ф., Шаповал Л.М. та ін. Роль ендотелію та біологічно-активних речовин ендотеліального походження в регуляції кровообігу та діяльності серця // Фізіол. журн. — 1997. — Т. 43, № 1–2. — С. 3-18.
Alvarez R., Gonzalez P., Batalla A. et al. Association between the NOS3 (-786 T/C) and the ACE (I/D) DNA genotypes and early coronary artery disease // Nitric. Oxide. — 2001. — Vol. 5, № 4. — P. 343-348.
Asmar R., Topouchian J., Pannier B. et al. Pulse wave velocity as endpoint in large-scale intervention trial (The Complior Study) // J. Hypertens. — 2001. — 19. — 813-18.
Bertrand M.E., Simoons M.L., Fox K.A.A. et al. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. The Task Force on the Management of Acute Coronary Syndromes of the European Society of Cardiology // Eur. Heart J. — 2002. — Vol. 23. — P. 1809-1840.
Braunwald E., Antman E.M., Brooks N.H. et al. ACC/AHA guidelines for the management of patients with unstable angina and non ST-elevation myocardial infarction: Executive summary and Recommendations. A report of the American College of Cardiology/ American Heart Association task force on practice guidelines (Committee on management of patients with unstable angina) // Circulation. — 2000. — Vol. 102. — P. 1193-1209.
Bredt D.S., Hwang P.M., Glatt C.E., Lowenstein C. et al. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase // Nature. — 1991. — Vol. 351. — P. 714-718.
Casas J.P., Bautista L.E., Humphries S.E., Hingorani A.D. Endothelial nitric oxide synthase genotype and ischemic disease. Meta-analysis of 26 studies involving 23028 subjects // Circulation. — 2004. — Vol. 109. — P. 1359-1365.
Colombo M.G., Paradossi U., Andreassi M.G. et al. Endothelial nitric oxide synthase gene polymorphisms and risk of coronary artery disease // Clin. Chem. — 2003. — Vol. 49. — P. 389-395.
Corretti M, Anderson T., Benjamin E. et al. Guidelines for the Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilatation of the Brahial Artery // J. Am. Coll. Cardiol. — 2002. — Vol. 39. — P. 257-265.
Doshi A., Lesinski A., Binkley P. A Promoter Polymorphism of the Endothelial Nitric Oxide Synthase Gene Reduces Endothelial Nitric Oxide Synthase Expression in Patients With Heart Failure // Circulation. — 2006. — Vol. 114. — P. 802.
Ghilardi G., Biondi M.L., DeMonti M. et al. Independent risk factor for moderate to severe internal carotid artery stenosis: T786C mutation of endothelial nitric oxide synthase gene // Clin. Chem. — 2002. — Vol. 48, № 7. — P. 989-993.
Gomma A.H., Elrayess M.A., Knight C.J. et al. The endothelial nitric oxide synthase (Glu298Asp and -786T > C) gene polymorphisms are associated with coronary in-stent restenosis // Eur. Heart J. — 2002. — Vol. 23. — P. 1955-1962.
Gregory Y.H. Effects of hormone-replacement therapy on hemostatic factors, lipid factors and endothelial functions in women undergoing surgical menopause: implications for prevention for atherosclerosis // Am. Heart J. —1997. — Vol. 134(4). — P. 164-771.
Harrison D.G. Cellular and molecular mechanisms of endothelial cell dysfunction // J. Clin. Invest. — 1997. — Vol. 19. — P. 23-27.
Hingorani A.D. Polymorphisms in endothelial nitric oxide synthase and atherogenesis: John French Lecture 2000 // Atherosclerosis. — 2001. — Vol. 154. — P. 521-527.
Hingorani A.D., Jia H., Stevens P.A. et al. A common variant in exon 7 of the endothelial constitutive nitric oxide synthase gene // Clin. Sci. — 1995. — Vol. 88. — P. 21.
Hohnloser S.H., Label M., Kasper W. et al. Assessment of coronary artery patency after thrombolytic therapy: accurte prediction utilizing the combined analysis of three noninvasive markers // J. Am. Coll. Cardiol. — 1991. — Vol. 18, № 1. — P. 44-49.
Hyndman M.E., Parsons H.G., Verma S. et al. The T-786®C mutation in endothelial nitric oxide synthase is associated with hypertension // Hypertension. — 2002. — Vol. 39. — P. 919-925.
Iwai N., Katsuya T., Ishikawa K. et al. Human prostacyclin synthase gene and hypertension: the Suita Study // Circulation. — 1999. — Vol. 100. — P. 2231-2236.
Janssens S.P., Shimouchi A., Quetermous T. et al. Cloning and expression of cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase // J. Biol. Chem. — 1992. — Vol. 267. — P. 14519-14522.
Jeerooburkhan N., Jones L.C., Bujac S. et al. Genetic and environmental determinants of plasma nitrogen oxides and risk of ischemic heart disease // Hypertension. — 2001. — Vol. 38. — P. 1054-1061.
Koenig W. Atherosclerosis involves more than just lipids: focus on inflammation // Eur. Heart J. — 1999. — Vol. 1 (suppl. T). — P. 19-26.
Kugiyama K., Yasue H., Ohgushi M. et al. Deficiency in nitric oxide bioactivity in epicardial coronary arteries of cigarette smokers // J. Amer. Coll. Cardiology. — 1996. — Vol. 28. — P. 1161-1167.
Lamas S., Marsden P.A., Li G.K. et al. Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform // Proc. Natl. Acad. Sci. USA. — 1992. — Vol. 89. — P. 6348-6352.
Lowenstein C.J., Glatt C.E., Bredt D.S., Snyder S.H. Cloned and expressed macrophage nitric oxide synthase contasts with the brain enzyme // Proc. Natl. Acad. Sci. USA. — 1992. — Vol. 89. — P. 6711-6715.
Luscher T.F., Tschudi M.R., Wenzel R.R., Noll G. Endotheliale dysfunktion und stickst off monoxid (NO; Nitric Oxide) // Internist. — 1997. — Vol. 38. — P. 411-419.
Marsden P.A., Heng H.H., Scherer S.W. et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene // J. Biol. Chem. — 1993. — Vol. 268. — P. 17478-17488.
Marsden P.A., Schappert K.T., Chen H.S. et al. Molecular cloning and characterization of human endothelial nitric oxide synthase // FEBS Lett. — 1992. — Vol. 307. — P. 287-293.
Moncada S., Palmer R.M.J., Higgs E.A. Nitric oxide: physiology, pathology and pharmacology // Pharmacol. Rev. — 1991. — Vol. 43. — P. 109-142.
Motoyama T., Kawano H., Kugiyama K. et al. Endothelium-dependent vasodilation in the brachial artery is impaired in smokers: effect of vitamin C // Amer. J. Physiology. — 1997. — Vol. 273. — P. 1644-1650.
Naber C.K., Siffert W., Erbe R., Heusch G. Genetics of human coronary vasomotion // Arch. Mal. Coeur. — 2004. — Vol. 97. — P. 255-260.
Naber C.K., Oldenburg O., Frey U. et al. Relevance of the T-786C and Glu298Asp variants in the endothelial nitric oxide synthase gene for cholinergic and adrenergic coronary vasomotor responses in man // Circulation. — 2003. — Vol. 106 (suppl. L). — P. 1042 (Abstract).
Nakayama M., Yasue H., Yoshimura M. et al. T-786®C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm // Circulation. — 1999. — Vol. 99. — P. 2864-2870.
Nakayama M., Yasue H., Yoshimura M. et al. T(-786)®C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene is associated with myocardial infarction, especially without coronary organic stenosis // Amer. J. Cardiology. — 2000. — Vol. 86, № 6. — P. 628-634.
Poirier O., Mao C., Mallet C. et al. Polymorphisms of the endothelial nitric oxide synthase gene — no consistent association with myocardial infarction in the ECTIM study // Eur. J. Clin. Invest. — 1999. — Vol. 29. — P. 284-290.
Ross R. Atherosclerosis — an inflammatory disease // New Engl. J. Med. — 1999. — Vol. 340. — P. 115-126.
Rossi G.P., Taddei S., Virdis A. et al. The T-786C and Glu298Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of Caucasian hypertensive patients // J. Amer. Coll. Cardiology. — 2003. — Vol. 41. — P. 938-945.
Sessa W.C. The nitric oxide synthase family of proteins // J. Vasc. Res. — 1994. — Vol. 31. — P. 131-143.
Song J., Yoon Y., Park K.U. et al. Genotype-specific influence on nitric oxide synthase gene expression, protein concentration, and enzyme activity in cultured human endothelial cells // Clin. Chem. — 2003. — Vol. 49, № 6. — P. 847-852.
Takagi S., Goto Y., Nonogi H. et al. Genetic Polymorphisms of angiotensin converting enzyme (I/D) and endothelial nitric oxide synthase (T(-788)C) genes in Japanese patients with myocardial infarction // Thromb Haemost. — 2001. — Vol. 86. — P. 1339-1340.
Tanus-Santos J.E., Desai M., Deak L.R. et al. Effects of endothelial nitric oxide synthase gene polymorphisms on platelet function, nitric oxide release, and interactions with estradiol // Pharmacogenetics. — 2002. — Vol. 12. — P. 407-413.
Tsukada T., Yokoyama K., Arai T. et al. Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite levels in humans // Biochem. Biophys. Res. Commun. — 1998. — Vol. 245. — P. 190-193.
Yoon Y., Song J., Hong S.H., Kim J.Q. Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease // Clin. Chem. — 2000. — Vol. 46, № 10. — P. 1626-1630.
Yoshimura M., Nakayama M., Shimasaki Y. et al. A T-786C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene and coronary arterial vasomotility // Amer. J. Cardiology. — 2000. — Vol. 85. — P. 710-714.
Yoshimura M., Yasue H., Nakayama M. et al. Genetic risk factors for coronary artery spasm: significance of endothelial nitric oxide synthase gene T-786C and missense Glu298Asp variants // J. Investig. Med. — 2000. — Vol. 48, № 5. — P. 367-374.
Zhang R., Min W., Sessa W.C. Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells // J. Biol. Chem. — 1995. — Vol. 270. — P. 15320-15326.
Downloads
Published
Issue
Section
License
Copyright (c) 2016 EMERGENCY MEDICINE

This work is licensed under a Creative Commons Attribution 4.0 International License.
Our edition uses the copyright terms of Creative Commons for open access journals.
Authors, who are published in this journal, agree with the following terms:
- The authors retain rights for authorship of their article and grant to the edition the right of first publication of the article on a Creative Commons Attribution 4.0 International License, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.
- Directing the article for the publication to the editorial board (publisher), the author agrees with transmitting of rights for the protection and using the article, including parts of the article, which are protected by the copyrights, such as the author’s photo, pictures, charts, tables, etc., including the reproduction in the media and the Internet; for distributing; for the translation of the manuscript in all languages; for export and import of the publications copies of the writers’ article to spread, bringing to the general information.
- The rights mentioned above authors transfer to the edition (publisher) for the unlimited period of validity and on the territory of all countries of the world.
- The authors guarantee that they have exclusive rights for using of the article, which they have sent to the edition (publisher). The edition (the publisher) is not responsible for the violation of given guarantees by the authors to the third parties.
- The authors have the right to conclude separate supplement agreements that relate to non-exclusive distribution of their article in the form in which it had been published in the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.
- The policy of the journal permits and encourages the publication of the article in the Internet (in institutional repository or on a personal website) by the authors, because it contributes to productive scientific discussion and a positive effect on efficiency and dynamics of the citation of the article.
- The rights to the article are deemed transferred by the authors to the edition (the publisher) since the moment of the publication of the article in the printed or electronic version of journal.