In the present study, we sought to evaluate the role of three polymorphisms in the ecNOS (endothelial constitutive nitric oxide synthase) gene in relation to the existence, severity and progression of CAD (coronary artery disease), MI (myocardial infarction) and the occurrence of ischaemia in a predominantly Caucasian population. Patients with CAD (n=760) and age- and sex-matched population-based controls (n=691) were genotyped for the −786T/C, E/D298 and 4a/b polymorphisms. Patients were randomized to pravastatin (40 mg) or placebo. Progression of atherosclerosis was evaluated by sequential angiography. Functionality was assessed by ST segment analysis of ambulant ECGs. The E298 (P=0.003) and 4a (P=0.001) alleles were associated with CAD. Furthermore, E298 (P=0.009) and −786T (P=0.022) alleles were associated with previous MI among patients, predominantly smokers. D/D298 homozygotes, but not −786T/C or 4a/4b mutants, had longer-lasting ischaemia than others (P<0.05). We found no differences in progression of atherosclerosis, irrespective of pravastatin use. We conclude that the E/D298 polymorphism is most consistently associated with CAD, but not with progression of atherosclerosis. The E allele is associated with CAD and MI, whereas the D allele is associated with ischaemia.
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September 2004
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Research Article|
August 24 2004
An integrated evaluation of endothelial constitutive nitric oxide synthase polymorphisms and coronary artery disease in men
Willem R. P. AGEMA;
Willem R. P. AGEMA
*Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
†Interuniversity Cardiology Institute The Netherlands, Utrecht, The Netherlands
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Moniek P. M. de MAAT;
Moniek P. M. de MAAT
‡Gaubius Laboratory, TNO PG, Leiden, The Netherlands
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Aeilko H. ZWINDERMAN;
Aeilko H. ZWINDERMAN
§Department of Medical Statistics, Academic Medical Center, Amsterdam, The Netherlands
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John J. P. KASTELEIN;
John J. P. KASTELEIN
∥Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
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Ton J. RABELINK;
Ton J. RABELINK
¶Department of Vascular Medicine and Nephrology, University Medical Center, Utrecht, The Netherlands
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Ad J. van BOVEN;
Ad J. van BOVEN
**Department of Cardiology, Academic Hospital Groningen, Groningen, The Netherlands
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Edith J. M. FESKENS;
Edith J. M. FESKENS
††Department of Chronic Diseases Epidemiology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands
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Jolanda M. A. BOER;
Jolanda M. A. BOER
††Department of Chronic Diseases Epidemiology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands
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Ernst E. van der WALL;
Ernst E. van der WALL
*Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
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J. Wouter JUKEMA
*Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
†Interuniversity Cardiology Institute The Netherlands, Utrecht, The Netherlands
Correspondence: Dr J. Wouter Jukema, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands (email [email protected]).
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Publisher: Portland Press Ltd
Received:
November 04 2003
Revision Received:
March 10 2004
Accepted:
April 06 2004
Accepted Manuscript online:
April 06 2004
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2004
Clin Sci (Lond) (2004) 107 (3): 255–261.
Article history
Received:
November 04 2003
Revision Received:
March 10 2004
Accepted:
April 06 2004
Accepted Manuscript online:
April 06 2004
Connected Content
This is a commentary on:
Resolving inconsistency in the results of genetic association studies of cardiovascular disease
Citation
Willem R. P. AGEMA, Moniek P. M. de MAAT, Aeilko H. ZWINDERMAN, John J. P. KASTELEIN, Ton J. RABELINK, Ad J. van BOVEN, Edith J. M. FESKENS, Jolanda M. A. BOER, Ernst E. van der WALL, J. Wouter JUKEMA; An integrated evaluation of endothelial constitutive nitric oxide synthase polymorphisms and coronary artery disease in men. Clin Sci (Lond) 1 September 2004; 107 (3): 255–261. doi: https://doi.org/10.1042/CS20030360
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