The Glu298→Asp (E298D; 894G→T) polymorphism of eNOS (endothelial nitric oxide synthase) has been related with cardiovascular disease. In the present study, we investigated the association of Glu298→Asp with atherosclerotic plaques in different carotid vessel segments and with carotid IMT (intima-media thickness). The Glu298→Asp eNOS polymorphism was determined by 5′-exonuclease assay among 2448 participants of the SHIP (Study of Health in Pomerania). Mean and maximum common carotid IMT, as well as carotid atherosclerosis, were measured by high-resolution ultrasound. The Asp/Asp298 genotype was associated with an increased risk of atherosclerotic plaques at the level of the common carotid arteries [multivariate odds ratio, 1.57 and 95% CI (confidence interval), 1.05–2.34; P=0.025], but not in the carotid bifurcations or internal or external carotid arteries. Glu298→Asp genotype was not associated with carotid IMT in the whole sample. However, the Asp/Asp298 genotype was independently associated with both higher mean [adjusted increase by 0.046 mm (95% CI, 0.013–0.078); P=0.006] and maximum carotid IMT [0.137 mm (95% CI, 0.064–0.209); P<0.001] in the low-risk group of subjects without carotid atherosclerosis. In conclusion, the Asp/Asp298 genotype is associated with atherosclerosis in the common carotid arteries and, in a low-risk group, also with carotid IMT. This suggests that the association of the Glu298→Asp genotype with atherosclerosis in the carotid arteries is site-specific and is modified by overall cardiovascular risk.
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November 2005
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Research Article|
October 24 2005
Endothelial nitric oxide synthase Glu298→Asp polymorphism, carotid atherosclerosis and intima-media thickness in a general population sample
Birger Wolff;
*Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany
Correspondence: Dr Birger Wolff (email birger.wolff@uni-greifswald.de).
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Claudia Braun;
Claudia Braun
†Institut für Pharmakologie, Peter Holtz Research Centre of Pharmacology and Experimental Therapeutics, Universität Greifswald, Greifswald, Germany
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Christina Schlüter;
Christina Schlüter
†Institut für Pharmakologie, Peter Holtz Research Centre of Pharmacology and Experimental Therapeutics, Universität Greifswald, Greifswald, Germany
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Hans J. Grabe;
Hans J. Grabe
‡Klinik für Psychiatrie und Psychotherapie, Universität Greifswald, Hanse Klinikum Stralsund, Stralsund, Germany
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Katrin Popowski;
Katrin Popowski
†Institut für Pharmakologie, Peter Holtz Research Centre of Pharmacology and Experimental Therapeutics, Universität Greifswald, Greifswald, Germany
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Henry Völzke;
Henry Völzke
§Institut für Epidemiologie und Sozialmedizin, Universität Greifswald, Greifswald
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Jan Lüdemann;
Jan Lüdemann
∥Institut für Klinische Chemie, Universität Greifswald, Greifswald, Germany
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Ulrich John;
Ulrich John
‡Klinik für Psychiatrie und Psychotherapie, Universität Greifswald, Hanse Klinikum Stralsund, Stralsund, Germany
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Ingolf Cascorbi
Ingolf Cascorbi
†Institut für Pharmakologie, Peter Holtz Research Centre of Pharmacology and Experimental Therapeutics, Universität Greifswald, Greifswald, Germany
¶Institut für Pharmakologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
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Clin Sci (Lond) (2005) 109 (5): 475–481.
Article history
Received:
March 14 2005
Revision Received:
June 20 2005
Accepted:
July 20 2005
Accepted Manuscript online:
July 20 2005
Citation
Birger Wolff, Claudia Braun, Christina Schlüter, Hans J. Grabe, Katrin Popowski, Henry Völzke, Jan Lüdemann, Ulrich John, Ingolf Cascorbi; Endothelial nitric oxide synthase Glu298→Asp polymorphism, carotid atherosclerosis and intima-media thickness in a general population sample. Clin Sci (Lond) 1 November 2005; 109 (5): 475–481. doi: https://doi.org/10.1042/CS20050090
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