CARDIOVASCULAR MEDICINE

Evidence 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

M G Colombo, M G Andreassi, U Paradossi, N Botto, S Manfredi, S Masetti, G Rossi, A Clerico, A Biagini

CNR Institute of Clinical Physiology, G Pasquinucci Hospital, Massa, Italy

Correspondence to:
Correspondence to:
Dr Maria Giovanna Colombo, CNR Institute of Clinical Physiology, G Pasquinucci Hospital, Via Aurelia SUD-Montepepe, 54100 Massa, Italy;
colombo{at}ifc.pi.cnr.it

Background: Genetic variants of endothelial nitric oxide synthase (eNOS) could influence individual susceptibility to coronary artery disease.

Objective: To assess whether Glu²⁹⁸Asp polymorphism of the eNOS gene is associated with the occurrence and severity of angiographically defined coronary artery disease in the Italian population.

Methods: Polymerase chain reaction/restriction fragment length polymorphism analysis was done to detect the Glu²⁹⁸Asp variant of the eNOS gene in 201 patients with coronary artery disease and 114 controls. The severity of coronary artery disease was expressed by the number of affected vessels and by the Duke scoring system.

Results: The frequencies of the eNOS Glu/Glu, Glu/Asp, and Asp/Asp genotypes in the coronary artery disease group were significantly different from those of controls (45.3%, 38.8%, and 15.9% v 42.1%, 51.8%, and 6.1%, respectively; ² = 8.589, p = 0.0136). In comparison with subjects who had a Glu²⁹⁸ allele in the eNOS gene, the risk of coronary artery disease was increased among Asp/Asp carriers (odds ratio 2.9, 95% confidence interval 1.2 to 6.8, p = 0.01) and was independent of the other common risk factors (p = 0.04). There was a significant association between the eNOS Glu²⁹⁸Asp variant and both the number of stenosed vessels (mean (SEM), 2.3 (0.1) for Asp/Asp v 1.9 (0.1) and 1.8 (0.1) for Glu/Glu and Glu/Asp, respectively; p = 0.01) and the Duke score (56.1 (3.1) for Asp/Asp v 46.7 (2.0) and 46.1 (1.9) for Glu/Glu and Glu/Asp, respectively; p = 0.02).

Conclusions: Glu²⁹⁸Asp polymorphism of the eNOS gene appears to be associated with the presence, extent, and severity of angiographically assessed coronary artery disease.

Keywords: coronary artery disease; nitric oxide; genetics

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Galluccio, E., Piatti, P., Citterio, L., Lucotti, P. C. G., Setola, E., Cassina, L., Oldani, M., Zavaroni, I., Bosi, E., Colombo, A., Alfieri, O., Casari, G., Reaven, G. M., Monti, L. D. (2008). Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis. Am. J. Physiol. Endocrinol. Metab. 294: E978-E986 [Abstract] [Full Text]  
• Casas, J. P., Cavalleri, G. L., Bautista, L. E., Smeeth, L., Humphries, S. E., Hingorani, A. D. (2006). Endothelial Nitric Oxide Synthase Gene Polymorphisms and Cardiovascular Disease: A HuGE Review. Am J Epidemiol 164: 921-935 [Abstract] [Full Text]  
• Kerkeni, M., Addad, F., Chauffert, M., Myara, A., Ben Farhat, M., Miled, A., Maaroufi, K., Trivin, F. (2006). Hyperhomocysteinemia, Endothelial Nitric Oxide Synthase Polymorphism, and Risk of Coronary Artery Disease. Clin. Chem. 52: 53-58 [Abstract] [Full Text]  
• Antoniades, C., Tousoulis, D., Vasiliadou, C., Pitsavos, C., Chrysochoou, C., Panagiotakos, D., Tentolouris, C., Marinou, K., Koumallos, N., Stefanadis, C. (2005). Genetic Polymorphism on Endothelial Nitric Oxide Synthase Affects Endothelial Activation and Inflammatory Response During the Acute Phase of Myocardial Infarction. J Am Coll Cardiol 46: 1101-1109 [Abstract] [Full Text]  
• Liu, Y., Burdon, K. P., Langefeld, C. D., Beck, S. R., Wagenknecht, L. E., Rich, S. S., Bowden, D. W., Freedman, B. I. (2005). T-786C Polymorphism of the Endothelial Nitric Oxide Synthase Gene Is Associated with Albuminuria in the Diabetes Heart Study. J. Am. Soc. Nephrol. 16: 1085-1090 [Abstract] [Full Text]  
• van Onna, M., Kroon, A. A., Houben, A. J.H.M., Koster, D., Zeegers, M. P.A., Henskens, L. H.G., Plat, A. W., Stoffers, H. E.J.H., de Leeuw, P. W. (2004). Genetic Risk of Atherosclerotic Renal Artery Disease: The Candidate Gene Approach in a Renal Angiography Cohort. Hypertension 44: 448-453 [Abstract] [Full Text]  
• Casas, J. P., Bautista, L. E., Humphries, S. E., Hingorani, A. D. (2004). Endothelial Nitric Oxide Synthase Genotype and Ischemic Heart Disease: Meta-Analysis of 26 Studies Involving 23028 Subjects. Circulation 109: 1359-1365 [Abstract] [Full Text]  
• Colombo, M. G., Paradossi, U., Andreassi, M. G., Botto, N., Manfredi, S., Masetti, S., Biagini, A., Clerico, A. (2003). Endothelial Nitric Oxide Synthase Gene Polymorphisms and Risk of Coronary Artery Disease. Clin. Chem. 49: 389-395 [Abstract] [Full Text]  
• (2002). Variant of endothelial nitric oxide synthase gene determines severity of atherosclerosis. J. Med. Genet. 39: 721-721 [Full Text]