Skip to main content
SpringerLink
Log in

The relationship between endothelial nitric oxide synthase gene polymorphism (T-786 C) and coronary artery disease in the Turkish population

  • ORIGINAL ARTICLE
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Previous studies revealed that there were various mutations on endothelial nitric oxide synthase (eNOS) gene and these mutations might be a risk factor for coronary artery disease (CAD), myocardial infarction (MI), and hypertension (HT). In this study, we aimed to investigate the relationship between eNOS gene polymorphism (T-786 C) and coronary artery disease in the Turkish population. Two hundred and eleven unrelated individuals (152 male, 59 female, mean age 59 years, range 27–85) whose angiographic examinations were performed in our hospital were enrolled into the study; 159 of these had angiographically determined coronary artery lesions (≥50% stenosis at least in one vessel). Fifty-two individuals were free of coronary artery disease on their coronary angiography. The Gensini scoring system was used to determine the severity of the CAD. The polymerase chain reaction (PCR) method was used for genotyping the individuals. To determine the independent risk factors for coronary artery disease, multivariate logistic regression analysis was used. The variant distribution of the T-786 C polymorphism was as follows. For all individuals: TT 94 (44.5%), TC 88 (41.7%), CC 29 (13.8%); in CAD patients: TT 63 (39.6%), TC 73 (45.9%), CC 23 (14.5%); and in normal individuals: TT 31 (59.6%), TC 15 (28.8%), CC 6 (11.5%). There was a statistically significant difference in the variant distribution between CAD and normal individuals (P < 0.05). On the other hand, when we compared the frequency of the at-least-one-C-allele carriers (CC+TC, dominant model) and TT homozygous, those with at least one C allele were more prevalent in CAD patients. The results were as follows. In coronary artery disease patients: CC+TC 96 (60.4%), TT 63 (39.6%); in normals: TC+CC 21 (40.4%), TT 31 (59.6%) (P < 0.01). When we compared the allele distribution (T vs C, additive model) between CAD patients and normal controls, the results were as follows: T 0.625 vs 0.740, C 0.375 vs 0.260; there was also a statistically significant association between CAD and C allele (P < 0.05). When we compared the means of the Gensini scores between each genotype of the T-786 C mutation, there was a statistically significant difference. The results were TT (48.6 ± 37.3, median 43.0), TC (55.4 ± 41.2, median 41.0), CC (77 ± 43.6, median 80.0) (P < 0.05). Multivariate logistic regression analysis revealed that C-dominant (CC+TC) individuals had 2.9-fold more likelihood to suffer from CAD (odds ratio: 2.902; confidence interval: 1.272–6.622) (P < 0.05). We conclude that the T-786 C polymorphism of eNOS gene might be a risk factor for coronary artery disease in the Turkish population.

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

Similar content being viewed by others

References

  1. S Moncada A Higgs (1993) ArticleTitleThe L-arginine-nitric oxide pathway N Engl J Med 329 2002–2012 Occurrence Handle10.1056/NEJM199312303292706 Occurrence Handle1:CAS:528:DyaK2cXhsF2ntrw%3D Occurrence Handle7504210

    Article  CAS  PubMed  Google Scholar 

  2. P Vallance J Collier S Moncada (1989) ArticleTitleEffects of endothelium-derived nitric oxide on peripheral arteriolar tone in man Lancet 2 997–1000 Occurrence Handle10.1016/S0140-6736(89)91013-1 Occurrence Handle1:CAS:528:DyaK3cXhvFentg%3D%3D Occurrence Handle2572793

    Article  CAS  PubMed  Google Scholar 

  3. AA Quyyumi N Dakak NP Andrews S Husain S Arora DM Gilligan JA Panza RO Cannon SuffixIII (1995) ArticleTitleNitric oxide activity in the human coronary circulation J Clin Invest 95 1747–1755 Occurrence Handle1:STN:280:ByqB387mt1w%3D Occurrence Handle7706483

    CAS  PubMed  Google Scholar 

  4. PL Huang Z Huang H Mashimo et al. (1995) ArticleTitleHypertension in mice lacking the gene for endothelial nitric oxide synthase Nature 377 239–242 Occurrence Handle10.1038/377239a0 Occurrence Handle1:CAS:528:DyaK2MXot1Gltbk%3D Occurrence Handle7545787

    Article  CAS  PubMed  Google Scholar 

  5. Y Ohashi S Kawashima K Hirata et al. (1998) ArticleTitleHypotension and reduced nitric-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase J Clin Invest 102 2061–2071 Occurrence Handle1:CAS:528:DyaK1MXmtFKg Occurrence Handle9854041 Occurrence Handle10.1172/JCI4394

    Article  CAS  PubMed  Google Scholar 

  6. HHHW Schmidt U Walter (1994) ArticleTitleNO at work Cell 78 9925 Occurrence Handle10.1016/0092-8674(94)90267-4

    Article  Google Scholar 

  7. AJ Cayatte JJ Palacino K Horten RA Cohen (1994) ArticleTitleChronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits Arterioscler Thromb 14 753–759 Occurrence Handle1:CAS:528:DyaK2cXltVGltbY%3D Occurrence Handle7513551

    CAS  PubMed  Google Scholar 

  8. EG Shesely N Maeda HS Kim et al. (1996) ArticleTitleElevated blood pressures in mice lacking endothelial nitric oxide syntase Proc Natl Acad Sci USA 93 13176–13181 Occurrence Handle10.1073/pnas.93.23.13176 Occurrence Handle1:CAS:528:DyaK28XmvV2qt7o%3D Occurrence Handle8917564

    Article  CAS  PubMed  Google Scholar 

  9. K Kugiyama H Yasue K Okumura H Ogawa K Fujimoto K Nakao M Yoshimura T Motoyama Y Inobe H Kawano (1996) ArticleTitleNitric oxide activity is deficient in spasm arteries of patients with coronary spatic angina Circulation 94 266–27 Occurrence Handle1:STN:280:BymA3Mvis1c%3D Occurrence Handle8759065

    CAS  PubMed  Google Scholar 

  10. EY Choi HM Kwon YW Yoon D Kim HS Kim (2004) ArticleTitleAssessment of extent of myocardial ischemia in patients with non-ST elevation acute coronary syndrome using serum B-type natriuretic peptide level Yonsei Med J 45 IssueID2 255–262 Occurrence Handle15118997

    PubMed  Google Scholar 

  11. M Yoshimura H Yasue M Nakayama Y Shimasaki H Sumida S Sugiyama et al. (1998) ArticleTitleA missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese Hum Genet 103 65–69 Occurrence Handle10.1007/s004390050785 Occurrence Handle1:CAS:528:DyaK1cXks12htro%3D Occurrence Handle9737779

    Article  CAS  PubMed  Google Scholar 

  12. AD Hingorani CF Liang J Fatibene A Lyon S Monteith A Parsons et al. (1999) ArticleTitleA common variant of the endothelial nitric oxide synthase (Glu298Asp) is a major risk factor for coronary artery disease in the UK Circulation 100 1515–1520 Occurrence Handle1:CAS:528:DyaK1MXmvVWhtL0%3D Occurrence Handle10510054

    CAS  PubMed  Google Scholar 

  13. Y Shimasaki H Yasue M Yoshimura M Nakayama K Kugiyama H Ogaaw et al. (1998) ArticleTitleAssociation of the missense Glu298 Asp varinat of the endothelial nitric oxide synthase gene with myocardial infarction J Am Coll Cardiol 31 1506–1510 Occurrence Handle10.1016/S0735-1097(98)00167-3 Occurrence Handle1:CAS:528:DyaK1cXktV2nu7k%3D Occurrence Handle9626827

    Article  CAS  PubMed  Google Scholar 

  14. K Hibi T Ishigami K Tamura S Mizushima N Nyui T Fujita et al. (1998) ArticleTitleEndothelial nitric oxide synthase gene polymorphism and acute myocardial infarction Hypertension 32 521–526 Occurrence Handle1:CAS:528:DyaK1cXmtlyjsLw%3D Occurrence Handle9740620

    CAS  PubMed  Google Scholar 

  15. MG Colombo MG Andreassi U Paradossi N Botto S Manfredi S Masetti et al. (2002) ArticleTitleEvidence for association of a common variant of the endothelial nitric oxide synthase gene (Glu298Asp polymorphism) to the presence, extent and severity of coronary artery disease Heart 87 525–528 Occurrence Handle10.1136/heart.87.6.525 Occurrence Handle1:CAS:528:DC%2BD38XmslOgtbk%3D Occurrence Handle12010932

    Article  CAS  PubMed  Google Scholar 

  16. MG Colombo U Paradossi MG Andreassi N Botto S Manfredi A Biagini A Clerico (2003) ArticleTitleEndothelial nitric oxide synthase gene polymorphisms and risk of coronary artery disease Clin Chem 49 3389–3395 Occurrence Handle10.1373/49.3.389

    Article  Google Scholar 

  17. Y Miyamoto Y Saito N Kajiyama et al. (1998) ArticleTitleEndothelial nitric oxide synthase gene is positively associated with essential hypertension Hypertension 32 3–8 Occurrence Handle1:CAS:528:DyaK1cXkvVOlu78%3D Occurrence Handle9674630

    CAS  PubMed  Google Scholar 

  18. ME Hyndman HG Parsons S Verma PJ Bridge S Edworthy C Jones E Lonn F Charbonneau TJ Anderson (2002) ArticleTitleThe T-786 C mutation in endothelial nitric oxide synthase is associated with hypertension Hypertension 39 919–922 Occurrence Handle10.1161/01.HYP.0000013703.07316.7F Occurrence Handle1:CAS:528:DC%2BD38XjtlGjs7k%3D Occurrence Handle11967250

    Article  CAS  PubMed  Google Scholar 

  19. N Kajiyama Y Saito Y Miyamoto et al. (2000) ArticleTitleLack of association between T-786 C mutation in the 5′-flanking region of the endothelial nitric oxide synthase gene and essential hypertension Hypertens Res 23 561–565 Occurrence Handle1:CAS:528:DC%2BD3cXptVahu7c%3D Occurrence Handle11131266

    CAS  PubMed  Google Scholar 

  20. GP Rossi M Cesari M Zanchetta S Colonna G Maiolino L Pedon M Cavallin P Maiolino AC Pessina (2003) ArticleTitleThe T-786 C 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 IssueID6 930–937 Occurrence Handle10.1016/S0735-1097(02)03012-7 Occurrence Handle1:CAS:528:DC%2BD3sXislejsLw%3D Occurrence Handle12651036

    Article  CAS  PubMed  Google Scholar 

  21. GP Rossi S Taddei A Virdis et al. (2003) ArticleTitleThe T-786 C and Glu298Asp polymorphisms of the endothelial nitric oxide synthase gene affect the forearm blood flow responses of Caucasian hypertensive patients J Am Coll Cardiol 41 938–945 Occurrence Handle10.1016/S0735-1097(02)03011-5 Occurrence Handle1:CAS:528:DC%2BD3sXislejsL0%3D Occurrence Handle12651037

    Article  CAS  PubMed  Google Scholar 

  22. M Nakayama H Yasue M Yoshimura et al. (1999) ArticleTitleT-786 C mutation in the 5′-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm Circulation 99 2864–2870 Occurrence Handle1:CAS:528:DyaK1MXjvFKgs70%3D Occurrence Handle10359729

    CAS  PubMed  Google Scholar 

  23. M Nakayama H Yasue M Yoshimura Y Shimasaki H Ogawa K Kugiyama Y Mizuno E Harada S Nakamura T Ito Y Saito Y Miyamoto Y Ogawa K Nakao (2000) ArticleTitleT-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 Am J Cardiol 86 IssueID6 628–634 Occurrence Handle10.1016/S0002-9149(00)01041-9 Occurrence Handle1:CAS:528:DC%2BD3cXmt1Wqt78%3D Occurrence Handle10980213

    Article  CAS  PubMed  Google Scholar 

  24. A Berdeli C Sekuri F Sirri Cam E Ercan A Sagcan I Tengiz E Eser M Akin (2005) ArticleTitleAssociation between the eNOS (Glu298Asp) and the RAS genes polymorphisms and premature coronary artery disease in a Turkish population Clin Chin Acta 351 IssueID1–2 87–94 Occurrence Handle10.1016/j.cccn.2004.08.015 Occurrence Handle1:CAS:528:DC%2BD2cXhtVant7zF

    Article  CAS  Google Scholar 

  25. Afrasyap L, Ozturk G (2004) Acta Biochim Biophys Sin (Shanghai). 36(10):661–666

  26. H Cine AC Hatemi N Erginel-Unaltuna (2002) ArticleTitleAssociation of a polymorphism of the ecNOS gene with myocardial infarction in a subgrup of Turkish MI patients Clin Genet 61 IssueID1 66–70 Occurrence Handle10.1034/j.1399-0004.2002.610113.x Occurrence Handle1:STN:280:DC%2BD383hslGqtQ%3D%3D Occurrence Handle11903359

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiology Department, Siyami Ersek Cardiovascular and Thoracic Surgery Center, Istanbul, Turkey

    Burak Tangurek, Nihat Ozer, Nurten Sayar, Sait Terzi, Hale Yilmaz, Sennur Unal Dayi, Huseyin Aksu, Recep Asilturk & Aydin Cagil

  2. Genlab Medical Diagnostics and Research Laboratory, Istanbul, Turkey

    Figen Ciloglu

Authors
  1. Burak Tangurek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nihat Ozer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nurten Sayar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sait Terzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hale Yilmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sennur Unal Dayi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Figen Ciloglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Huseyin Aksu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Recep Asilturk
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Aydin Cagil
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Burak Tangurek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tangurek, B., Ozer, N., Sayar, N. et al. The relationship between endothelial nitric oxide synthase gene polymorphism (T-786 C) and coronary artery disease in the Turkish population. Heart Vessels 21, 285–290 (2006). https://doi.org/10.1007/s00380-005-0902-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-005-0902-0

Key words

Search

Navigation