Skip to main content
SpringerLink
Log in

Relationship between hemorheology and Glu(298)Asp polymorphism of endothelial nitric oxide synthase gene in patients with coronary artery disease

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

This study aimed to investigate the relationship between endothelial nitric oxide synthase Glu(298)Asp gene polymorphism and hemorheological parameters. Red blood cell (RBC) deformability, aggregation were measured using an ectacytometry, whole blood, plasma viscosities were determined by a viscometer. Restriction fragment length polymorphism was used to detect polymorphism. Plasma nitrite, nitrate concentrations were determined by Griess method. The genotype distribution of the control group was as follows: 50 (67.5%) GG, 21 (28.4%) GT, 3 (4.1%) TT. A 48 (57.8%) of the patients with CAD had GG, 28 (33.7%) GT, 7 (8.5%) of them TT genotype. RBC aggregation index of CAD patients with G allele was higher and t½ lower compared to controls carrying the same allele. The amplitude of RBC aggregation of healthy subjects with T allele, who are under increased cardiovascular risk was lower compared to control subjects with G allele. The results of this study indicate that, alterations in RBC aggregation seem to be a consequence of CAD, more than being a preexisting cause. Additionally, some compensatory mechanisms by causing decrements in RBC aggregation, may help regulation of circulation in healthy individuals with high cardiovascular risk.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Madamanchi NR, Tchivilev I, Runge M (2006) Genetic markers of oxidative stress and coronary atherosclerosis. Curr Atheroscler Rep 8:177–183

    Article  CAS  PubMed  Google Scholar 

  2. Lloyd-Jones DM, Bloch KD (1996) The vascular biology of nitric oxide and its role in atherogenesis. Annu Rev of Med 47:365–375

    Article  CAS  Google Scholar 

  3. Colombo MG, Paradossi U, Andreassi MG et al (2003) Endothelial nitric oxide synthase gene polymorphisms and risk of coronary artery disease. Clin Chem 49:389–395

    Article  CAS  PubMed  Google Scholar 

  4. Tangurek B, Ozer N, Sayar N et al (2006) The relationship between endothelial nitric oxide synthase gene polymorphism (T-786 C) and coronary artery disease in the Turkish population. Heart Vessel 21:285–290

    Article  Google Scholar 

  5. Berdeli A, Sekuri C, Cam SF et al (2005) Association between the eNOS (Glu298Asp) and the RAS genes polymorphisms and premature coronary artery disease in a Turkish population. Clin Chim Acta 351:87–94

    Article  CAS  PubMed  Google Scholar 

  6. Srivastava K, Biswas UK, Narang R et al (2005) Prevalence of eNOS Glu298Asp polymorphism in healthy volunteers from a region of Northern India. Community Genet 8:180–183

    Article  PubMed  Google Scholar 

  7. Cam SF, Sekuri C, Tengiz I et al (2005) The G894T polymorphism on endothelial nitric oxide synthase gene is associated with premature coronary artery disease in a Turkish population. Thromb Res 116:287–292

    Article  CAS  PubMed  Google Scholar 

  8. Kesmarky G, Toth K, Habon L et al (1998) Hemorheological parameters in coronary artery disease. Clin Hemorheol Microcirc 18:245–251

    CAS  PubMed  Google Scholar 

  9. Lowe GD, Drummond MM, Lorimer AR et al (1980) Relation between extent of coronary artery disease and blood viscosity. Br Med J 280:673–674

    Article  CAS  PubMed  Google Scholar 

  10. Weng X, Cloutier G, Genest J Jr (1999) Contribution of the −455G/A polymorphism at the beta-fibrinogen gene to erythrocyte aggregation in patients with coronary artery disease. Thromb Haemost 82:1406–1411

    CAS  PubMed  Google Scholar 

  11. Becker RC (1993) The role of blood viscosity in the development and progression of coronary artery disease. Cleve Clin J Med 60:353–358

    CAS  PubMed  Google Scholar 

  12. Montalescot G, Collet JP, Choussat R et al (1998) Fibrinogen as a risk factor for coronary heart disease. Eur Heart J 19(Suppl H):H11–H17

    CAS  PubMed  Google Scholar 

  13. Berliner S, Rogowski O, Aharonov S et al (2005) Erythrocyte adhesiveness/aggregation: a novel biomarker for the detection of low-grade internal inflammation in individuals with atherothrombotic risk factors and proven vascular disease. Am Heart J 149:260–267

    Article  CAS  PubMed  Google Scholar 

  14. Boss N, Wietelmann H, Bierner M et al (1980) Red blood cell aggregation in men with coronary artery disease. Eur J Cardiol 12:47–54

    CAS  PubMed  Google Scholar 

  15. Rainer C, Kawanishi DT, Chandraratna PA et al (1987) Changes in blood rheology in patients with stable angina pectoris as a result of coronary artery disease. Circulation 76:15–20

    CAS  PubMed  Google Scholar 

  16. Miyamoto Y, Saito Y, Nakayama M et al (2000) Replication protein A1 reduces transcription of the endothelial nitric oxide synthase gene containing a −786T → C mutation associated with coronary spastic angina. Hum Mol Genet 9:2629–2637

    Article  CAS  PubMed  Google Scholar 

  17. Hardeman MR, Goedhart PT, Dobbe JGG et al (1994) Laser assisted optical rotational cell analyzer (LORCA): a new instrument for measurement of various structural hemorhelogical parameters. Clin Hemorheol 14:605–618

    Google Scholar 

  18. Hardeman MR, Dobbe JG, Ince C et al (2001) The laser-assisted optical rotational cell analyzer (LORCA) as red blood cell aggregometer. Clin Hemorheol Microcirc 25:1–11

    CAS  PubMed  Google Scholar 

  19. Pasaoglu H, Bulduk G, Ogus E et al (2004) Nitric oxide, lipid peroxides, and uric acid levels in pre-eclampsia and eclampsia. Tohoku J Exp Med 202:87–92

    Article  CAS  PubMed  Google Scholar 

  20. Liakopoulos OJ, Dorge H, Popov AF (2006) Influence of eNOS gene polymorphisms (894G/T-786/T) on postoperative hemodynamics after cardiac surgery. Thorac Cardiovasc Surg 54:233–238

    Article  CAS  PubMed  Google Scholar 

  21. Afrasyap L, Ozturk G (2004) NO level and endothelial NO synthase gene polymorphism (Glu298Asp) in the patients with coronary artery disease from the Turkish population. Acta Biochim Biophys Sin (Shanghai) 36:661–666

    Article  CAS  Google Scholar 

  22. Yoon Y, Song J, Hong SH et al (2000) Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease. Clin Chem 46:1626–1630

    CAS  PubMed  Google Scholar 

  23. Nagassaki S, Metzger IF, Souza-Costa DC et al (2005) eNOS genotype is without effect on circulating nitrite/nitrate level in healthy male population. Thromb Res 115:375–379

    Article  CAS  PubMed  Google Scholar 

  24. Stuart J, Nash GB (1990) Red cell deformability and haematological disorders. Blood Rev 4:141–147

    Article  CAS  PubMed  Google Scholar 

  25. Penco M, Romano S, Dagianti A Jr et al (2000) Modifications of whole blood filterability during acute myocardial infarction. Clin Hemorheol Microcirc 22:153–159

    CAS  PubMed  Google Scholar 

  26. Low J, Dodds AJ, McGrath M et al (1985) Red cell deformability and other haemorheological variables in stable coronary artery disease. Thromb Res 38:269–276

    Article  CAS  PubMed  Google Scholar 

  27. Alexandratou E, Yova D, Cokkinos DV et al (1999) Morphometric characteristics of red blood cells as diagnostic factors for coronary artery disease. Clin Hemorheol Microcirc 21:383–388

    CAS  PubMed  Google Scholar 

  28. Larsson H, Gustavsson CG, Odeberg H et al (1988) Increased whole blood and plasma viscosity in patients with angina pectoris and “normal” coronary arteries. Acta Med Scand 224:109–114

    CAS  PubMed  Google Scholar 

  29. Rampling MW (1988) Clinical blood rheology. In: Lowe GDO (ed) Red cell aggregation and yield stress. CRC Press, Boca Raton, pp 45–64

    Google Scholar 

  30. Pfafferott C, Moessmer G, Ehrly AM, Bauersachs RM (1999) Involvement of erythrocyte aggregation and erythrocyte resistance to flow in acute coronary syndromes. Clin Hemorheol Microcirc 21:35–43

    CAS  PubMed  Google Scholar 

  31. Meiselman HJ (1999) Hemorheologic alterations in hypertension: chicken or egg? Clin Hemorheol Microcirc 21:195–200

    CAS  PubMed  Google Scholar 

  32. Rampling MW, Meiselman HJ, Neu B et al (2004) Influence of cell-specific factors on RBC aggregation. Biorheology 41:91–112

    CAS  PubMed  Google Scholar 

  33. Chien S (1987) Red cell deformability and its relevance to blood flow. Ann Rev Physiol 49:177–192

    Article  CAS  Google Scholar 

  34. Razavian SM, Del Pino M, Simon A et al (1992) Increase in erythrocyte disaggregation shear stress in hypertension. Hypertension 20:247–252

    CAS  PubMed  Google Scholar 

  35. Schmid-Schönbein H (1988) Clinical blood rheology. In: Lowe GDO (ed) Fluid dynamics and hemorheology in vivo: the interactions of hemodynamic parameters and hemorheological “properties” in determining the flow behavior of blood in microvascular networks. CRC Press, Boca Raton, pp 129–219

    Google Scholar 

Download references

Acknowledgments

This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) through project number [107S130 (SBAG-HD-225)]. The authors are thankful to Dr. Gulten Erken, Dr. Vural Kucukatay and Nagihan Cakir for their valuable help.

Author information

Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Pamukkale University, 20020, Kinikli, Denizli, Turkey

    Melek Bor-Kucukatay

  2. Department of Biochemistry, Faculty of Medicine, Pamukkale University, Kinikli, Denizli, Turkey

    Suleyman Demir

  3. Biochemistry Laboratory, Ceylanpınar State Hospital, Ceylanpınar, Şanlıurfa, Turkey

    Ramazan Akbay

  4. Department of Cardiology, Faculty of Medicine, Pamukkale University, Kinikli, Denizli, Turkey

    Dursun Dursunoglu & Ender Semiz

  5. Department of Biostatistics, Faculty of Medicine, Pamukkale University, Kinikli, Denizli, Turkey

    Beyza Akdag

Authors
  1. Melek Bor-Kucukatay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suleyman Demir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ramazan Akbay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dursun Dursunoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Beyza Akdag
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ender Semiz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Melek Bor-Kucukatay.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bor-Kucukatay, M., Demir, S., Akbay, R. et al. Relationship between hemorheology and Glu(298)Asp polymorphism of endothelial nitric oxide synthase gene in patients with coronary artery disease. Mol Biol Rep 37, 171–178 (2010). https://doi.org/10.1007/s11033-009-9572-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-009-9572-9

Keywords

Search

Navigation