HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Paolo Rossi, G. Articles by Pessina, A. C. Search for Related Content PubMed PubMed Citation Articles by Paolo Rossi, G. Articles by Pessina, A. C.

CLINICAL STUDY: POLYMORPHISMS AND CARDIOVASCULAR DISEASE

The T^-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study

Gian Paolo Rossi, MD, FACC, FAHA^,*, Maurizio Cesari, MD, Mario Zanchetta, MD^*, Stefania Colonna, MD, Giuseppe Maiolino, MD, Luigi Pedon, MD^*, Martina Cavallin, BiolD, Pietro Maiolino, MD^* and Achille C. Pessina, MD, PhD

^* Servizio di Emodinamica and Divisione di Cardiologia Ospedale di Cittadella, University of Padova, Padova, Italy
Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Padova, Italy

Manuscript received March 13, 2002; revised manuscript received October 7, 2002, accepted November 22, 2002.

^* Reprint requests and correspondence: Prof. Gian Paolo Rossi, Department of Clinical and Experimental Medicine, Clinica Medica 4 University Hospital, via Giustiniani, 2, 35126 Padova, Italy.
gianpaolo.rossi{at}unipd.it

OBJECTIVES: We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD).

BACKGROUND: Endothelial dysfunction foretells cardiovascular events and can be genetically determined.

METHODS: We genotyped for the promoter (T^-786C) and exon 7 (Glu298Asp, G⁸⁹⁴T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5'- and 3'-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T^-786C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD.

RESULTS: The overall genotype distribution of T^-786C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T^-786C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T^-786C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041).

CONCLUSIONS: The C allele at the T^-786C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.

Abbreviations and Acronyms   CAD   coronary artery disease   CV   cardiovascular   eNOS   endothelial nitric oxide synthase   GENICA   Genetic and ENvironmental Factors in Coronary Atherosclerosis study   HDL   high-density lipoprotein   LDL   low-density lipoprotein   MI   myocardial infarction   NO   nitric oxide

This article has been cited by other articles:

				G. Maiolino, M. Cesari, D. Sticchi, M. Zanchetta, L. Pedon, K. Antezza, A. C. Pessina, and G. P. Rossi Plasma Adiponectin for Prediction of Cardiovascular Events and Mortality in High-Risk Patients J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3333 - 3340. [Abstract] [Full Text] [PDF]

				I. Zineh, A. L. Beitelshees, and M. J. Haller NOS3 Polymorphisms Are Associated With Arterial Stiffness in Children With Type 1 Diabetes Diabetes Care, March 1, 2007; 30(3): 689 - 693. [Abstract] [Full Text] [PDF]

				J. P. Casas, G. L. Cavalleri, L. E. Bautista, L. Smeeth, S. E. Humphries, and A. D. Hingorani Endothelial Nitric Oxide Synthase Gene Polymorphisms and Cardiovascular Disease: A HuGE Review Am. J. Epidemiol., November 15, 2006; 164(10): 921 - 935. [Abstract] [Full Text] [PDF]

				A. Ahsan, G. Mohd, T. Norboo, M. A. Baig, and M. A. Q. Pasha Heterozygotes of NOS3 Polymorphisms Contribute to Reduced Nitrogen Oxides in High-Altitude Pulmonary Edema. Chest, November 1, 2006; 130(5): 1511 - 1519. [Abstract] [Full Text] [PDF]

				G. P. Rossi, G. Maiolino, M. Zanchetta, D. Sticchi, L. Pedon, M. Cesari, D. Montemurro, R. De Toni, S. Zavattiero, and A. C. Pessina The T-786C Endothelial Nitric Oxide Synthase Genotype Predicts Cardiovascular Mortality in High-Risk Patients J. Am. Coll. Cardiol., September 19, 2006; 48(6): 1166 - 1174. [Abstract] [Full Text] [PDF]

				E.J.F. Danson, Y.H. Zhang, C.E. Sears, A.R. Edwards, B. Casadei, and D.J. Paterson Disruption of inhibitory G-proteins mediates a reduction in atrial {beta}-adrenergic signaling by enhancing eNOS expression Cardiovasc Res, September 1, 2005; 67(4): 613 - 623. [Abstract] [Full Text] [PDF]

				Y. Liu, K. P. Burdon, C. D. Langefeld, S. R. Beck, L. E. Wagenknecht, S. S. Rich, D. W. Bowden, and B. I. Freedman T-786C Polymorphism of the Endothelial Nitric Oxide Synthase Gene Is Associated with Albuminuria in the Diabetes Heart Study J. Am. Soc. Nephrol., April 1, 2005; 16(4): 1085 - 1090. [Abstract] [Full Text] [PDF]

				M. Cesari, M. Zanchetta, A. Burlina, L. Pedon, G. Maiolino, D. Sticchi, A. C. Pessina, and G. P. Rossi Hyperhomocysteinemia Is Inversely Related With Left Ventricular Ejection Fraction and Predicts Cardiovascular Mortality in High-Risk Coronary Artery Disease Hypertensives Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 115 - 121. [Abstract] [Full Text] [PDF]

				M. Cattaruzza, T. J. Guzik, W. Slodowski, A. Pelvan, J. Becker, M. Halle, A. B. Buchwald, K. M. Channon, and M. Hecker Shear Stress Insensitivity of Endothelial Nitric Oxide Synthase Expression as a Genetic Risk Factor for Coronary Heart Disease Circ. Res., October 15, 2004; 95(8): 841 - 847. [Abstract] [Full Text] [PDF]

				M. van Onna, A. A. Kroon, A. J.H.M. Houben, D. Koster, M. P.A. Zeegers, L. H.G. Henskens, A. W. Plat, H. E.J.H. Stoffers, and P. W. de Leeuw Genetic Risk of Atherosclerotic Renal Artery Disease: The Candidate Gene Approach in a Renal Angiography Cohort Hypertension, October 1, 2004; 44(4): 448 - 453. [Abstract] [Full Text] [PDF]

				G. P. Rossi, G. Maiolino, J. P. Casas, A. D. Hingorani, S. E. Humphries, L. Smeeth, and L. E. Bautista Do Meta-Analyses of Association Studies of Endothelial Nitric Oxide Synthase Variants and Ischemic Heart Disease Provide Conclusive Answers? * Response Circulation, September 14, 2004; 110(11): e305 - e306. [Full Text] [PDF]

				T. Awata, T. Neda, H. Iizuka, S. Kurihara, T. Ohkubo, N. Takata, M. Osaki, M. Watanabe, Y. Nakashima, T. Sawa, et al. Endothelial Nitric Oxide Synthase Gene Is Associated With Diabetic Macular Edema in Type 2 Diabetes Diabetes Care, September 1, 2004; 27(9): 2184 - 2190. [Abstract] [Full Text] [PDF]

				E. J. F. Danson, K. S. Mankia, S. Golding, T. Dawson, L. Everatt, S. Cai, K. M. Channon, and D. J. Paterson Impaired regulation of neuronal nitric oxide synthase and heart rate during exercise in mice lacking one nNOS allele J. Physiol., August 1, 2004; 558(3): 963 - 974. [Abstract] [Full Text] [PDF]

				G. P. Rossi and G. Maiolino Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors J. Am. Coll. Cardiol., July 7, 2004; 44(1): 209 - 209. [Full Text] [PDF]

				U. Paradossi, E. Ciofini, A. Clerico, N. Botto, A. Biagini, and M. G. Colombo Endothelial Function and Carotid Intima-Media Thickness in Young Healthy Subjects Among Endothelial Nitric Oxide Synthase Glu298->Asp and T-786->C Polymorphisms Stroke, June 1, 2004; 35(6): 1305 - 1309. [Abstract] [Full Text] [PDF]

				G. P. Rossi and G. Maiolino Letter to the Editor: T-786C and G894T Variants of the Endothelial Nitric Oxide Synthase Gene and Training-Induced Correction of Endothelial Dysfunction in Coronary Artery Disease Patient Arterioscler. Thromb. Vasc. Biol., February 1, 2004; 24(2): e11 - 11. [Full Text]

				B. Voetsch and J. Loscalzo Genetic Determinants of Arterial Thrombosis Arterioscler. Thromb. Vasc. Biol., February 1, 2004; 24(2): 216 - 229. [Abstract] [Full Text]

				G. P. Rossi, M. Cesari, R. De Toni, M. Zanchetta, G. Maiolino, L. Pedon, C. Ganzaroli, P. Maiolino, and A. C. Pessina Antibodies to Oxidized Low-Density Lipoproteins and Angiographically Assessed Coronary Artery Disease in White Patients Circulation, November 18, 2003; 108(20): 2467 - 2472. [Abstract] [Full Text] [PDF]

				G. Maiolino, G. P. Rossi, D. M. McNamara, M. Bedi, R. Holubkov, L. Postava, R. Ramani, K. Janosko, M. Mathier, G. A. MacGowan, et al. Effect of the Asp298 Variant of Endothelial Nitric Oxide Synthase on Survival for Patients With Congestive Heart Failure * Response Circulation, October 14, 2003; 108 (15): e112 - e112. [Full Text] [PDF]

				A. Batalla, J. R. Reguero, and E. Coto The T-786C endothelial nitric oxide synthase genotype and coronary artery disease J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1140 - 1140. [Full Text] [PDF]

				G. P. Rossi, M. Cesari, and A. C. Pessina The T-786C endothelial nitric oxide synthase genotype and coronary artery disease: Reply J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1140 - 1141. [Full Text] [PDF]