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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2010; 56(1): 22-29

Influence of endothelial nitric oxide synthase T-786→C-promoter polymorphism on integral parameters of functional condition of arterial vessels

A.N. Parkhomenko, Ya.M. Lutay, V.E. Dosenko, V.L. Gurianova, A.A. Moibenko, A.Skarzevskiy.

  1. National Scientific Center «M.D. Strazhesko Institute of Cardiology”, Medical Academy of Sciences of Ukraine, Kyiv, Ukraine
  2. O.O.Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine


Frequency of eNOS T786->C promoter polymorphism in 325 patients with acute coronary syndrome and 104 control per­sons and influence of this polymorphism on reactive hyper­emia and arterial stiffness were determined. Interrelation be­tween T/T homozygous, T/C heterozygous and C/C homozygous was 42,5%, 41,2% and 16,3%, correspondingly (in control - 40,4%, 53,8% and 5,8%; P<0.01 by X2-test). Higher degree of brachial arteries diameter increase in response to ischemia was estimated in patients with T/T genotype: 8,03 ± 0,71% compared to 5,55 ± 0,92 % in Т/С (P<0.05) and 5,30 ± 1,21 % in C/C genotypes (P<0.05). Speed of pulse wave spreading on carotid-radial and carotid-femoral arteries segments was also depended on patients genotype: in T/T genotype was 9,10 ± 0,15 and 8,68 ± 0,26 correspondingly, in T/C - 9,38 ± 0,18 and 8,74 ± 0,21, and in C/C carriers - 9,71 ± 0,22 and 10,02 ± 0,71 (P<0.05). Thus, the data obtained indi­cate on significant influence of T786->C polymorphism on integral parameters of functional condition of arterial vessels.

Keywords: allelic polymorphism, endothelial NO-synthase,endothelial dysfunction, speed of pulse wave arrival frequency,acute coronary syndrome.


  1. 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. 5, N 4. P. 343-348. CrossRef PubMed
  3. 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. P. 813-818. CrossRef PubMed
  5. 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. 23. P. 1809-1840. CrossRef PubMed
  7. 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. AmericanHeart Association task force on practice guidelines (Committee on management of patients with unstable angina) . Circulation. 2000. 102. P. 1193-1209. CrossRef  
  8. Bredt D.S., Hwang P.M., Glatt C.E. et al. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase . Nature. 1991. 351. P. 714-718. CrossRef PubMed
  10. 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. 109. P. 1359-1365. CrossRef PubMed
  12. 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. 49. P. 389-395. CrossRef PubMed
  14. Corretti M, Anderson T., Benjamin E. et al. Guidelines for the ultrasound assessment of endothelial-depen-dent flow-mediated vasodilatation of the brahial artery . J. Amer. Coll. Cardiol. 2002. 39. P. 257-265. CrossRef  
  15. Dosenko V.E., Zagoriy V.Yu., Haytovich N.V., Gordok O.A., Moibenko A.A. Allelic polymorphism of endothe­lial NO-synthase gene and its functional manifestations . Acta Biochem. Pol. 2006. 53, N 2. P. 299-302.
  17. Dosenko V.E., Zagoriy V.Yu., Lutay Ya.M. et al. Allelic polymorphism of promoter (T7%C), but not that of exon 7 (G8^T) or VNTR in intron 4 of the endothelial nitric oxide synthase gene is positively associated with acute coronary syndrome in the Ukrainian population . Exp. Clin. Cardiol. 2006. 11, N 1. P. 11-13.
  19. Dosenko V.E., Lutay Ya. M, Zagoriy V.Yu. et al. [Fre­quencies of allelic polymorphism of endothelial NO-synthase gene in patients with acute coronary syn­drome in Ukrainian population] . Tsitol Genet. 2005, Mar-Apr. 39, N 2. P. 49-54.
  21. Dosenko V.E., Zahoriy V.Yu, Khaytovych N.V et al. [Allelic polymorphism of endothelial NO-synthase gene and its functional activity] . Fiziol. Zh. 2005. 51, N 2. P. 39-45.
  23. Dosenko V E., Zahoriy V Yu, Lutay Ya.M. et al. [Allelic polymorphism of endothelial NO-synthase (T(-786) >C) promoter gene as risk factor of acute coronary syn­drome] . Fiziol. Zh. 2005. 51, N 1. P. 72-76.
  25. Dosenko V.E., Zahoriy V.Yu, Moibenko A.A., Parkhomenko O.M. [Pathophysiologic aspects of endothelial NO-synthase genetic polymorphism] . Ibid. 2002. 48, N 6. P. 86-102.
  27. 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. 114. P. 802.
  29. Erbs S., Baither Y, Linke A. et al. Promoter but not exon polymorphism of endothelial nitric oxide synthase af­fects training-induced correction of endothelial dysfunc­tion . Arterioscler. Thromb. Vasc. Biol. 2003. 23. P. 1814-1819. CrossRef PubMed
  31. 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. 48, N 7. P. 989-993.
  33. 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. 23. P. 1955-1962. CrossRef PubMed
  35. Harrison D.G. Cellular and molecular mechanisms of endothelial cell dysfunction . J. Clin. Invest. 1997. 19. P. 23-27.
  37. 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. 39. P. 919-925. CrossRef PubMed
  39. Iwai N., Katsuya T., Ishikawa K. et al. Human prostacyclin synthase gene and hypertension: the Suita Study . Circulation. 1999. 100. P. 2231-2236. CrossRef PubMed
  41. 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. 38. P. 1054-1061. CrossRef PubMed
  43. Luscher T.F., Tschudi M.R., Wenzel R.R., Noll G. Endothelial dysfunktion und stickst off monoxid (NO; Nitric Oxide) . Internist. 1997. 38. P. 411-419. CrossRef PubMed
  45. Moibenko O.O, Pavliuchenko VB, Datsenko V.V. et al. [The role of endothelium-dependent factors in realizing cardiogenic reflexes under normal and patho­logical conditions] . Fiziol. Zh. 2000. 46, N 2. P. 19-32.
  47. Moibenko O.O., Sahach V.F., Shapoval L.M. et al. [The role of the endothelium and of biologically active sub­stances of endothelial origin in regulating blood circu­lation and cardiac activity] . Ibid. 1997. 43, N 1-2. P. 3-18.
  49. Moncada S., Palmer R.M.J., Higgs E.A. Nitric oxide: physiology, pathology and pharmacology . Pharmacol. Rev. 1991. 43. P. 109-142.
  51. 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. 273. P. 1644-1650. CrossRef PubMed
  53. 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. 106 (Suppl. L). P. 1042.
  55. Naber C.K., Siffert W., Erbe R., Heusch G. Genetics of human coronary vasomotion . Arch. Mal. Coeur. 2004. 97. P. 255-260.
  57. 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. 86, N 6. P. 628-634. CrossRef  
  58. Nakayama M., Yasue H., Yoshimura M. et al. T-786. Cmutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm . Circulation. 1999. 99. P. 2864-2870. CrossRef PubMed
  60. Parkhomenko A.N., Lutay Ya.M., Dosenko V.E. et al. Prevalence, pathogenetic and prognostic significance of polymorphism of endothelial NO synthase gene in patients with acute coronary syndrome . Ukr. Kar-diol. J. 2005. N 4. P. 20-27.
  62. 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. 29. P. 284-290. CrossRef PubMed
  64. 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. 41. P. 938-945. CrossRef  
  65. Sessa W.C. The nitric oxide synthase family of pro­teins . J. Vasc. Res. 1994. 31. P. 131-143. CrossRef PubMed
  67. 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. 49, N 6. P. 847-852. CrossRef PubMed
  69. 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. 86. P. 1339-1340. CrossRef PubMed
  71. 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. 12. P. 407-413. CrossRef PubMed
  73. 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. 85. P. 710-714. CrossRef  
  74. 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. 48, N 5. P. 367-374.
  76. 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. 270. P. 15320-15326. CrossRef PubMed

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