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Received on January 26, 2005
Accepted on April 27, 2005
Hemostasis and Thrombosis |
1 Department of Medical and Surgical Critical Care, and Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy, and Center for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy
2 Department of Clinical Pathophysiology, Unit of Nutrition, University of Florence, Florence, Italy
* To whom correspondence should be addressed. E-mail: cinziafatini{at}hotmail.com.
Background: Nitric oxide (NO) plays a relevant role in various events during atherogenesis. In vitro data suggest that NO may modulate homocysteine (Hcy) concentrations. The aim of this study was to investigate the role of endothelial nitric oxide synthase (eNOS) -786T>C, 894G>T, and 4a4b polymorphisms in influencing Hcy concentrations.
Methods: Blood samples were obtained from 1287 unrelated persons. Plasma Hcy was measured by fluorescence polarization immunoassay, folate and vitamin B12 by RIA, vitamin B6 by HPLC, and eNOS and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms by PCR with restriction fragment length polymorphism analysis. %Results: MTHFR 677C>T polymorphism significantly influenced Hcy concentrations after adjustment for all confounding variables (P <0.0001 for trend). Univariate analysis showed that the eNOS -786T>C polymorphism, but not 894G>T and 4a4b, was significantly associated with the risk of having Hcy in the third tertile [>13.4 µmol/L; odds ratio (OR) = 1.2; 95% confidence interval (CI), 1.02-1.5; P = 0.03]. After adjustment for all variables known to influence Hcy, the -786T>C polymorphism still influenced Hcy concentrations (OR = 1.9; 95% CI, 1.1-3.2; P = 0.01). By analyzing the influence of eNOS polymorphisms on plasma Hcy concentrations according to vitamin concentrations (folate, vitamin B6, and vitamin B12), age, and smoking habits, we found a significant association between the eNOS -786T>C polymorphism and Hcy in nonsmokers, in persons with normal vitamin status, and in persons <60 years.
Conclusion: The eNOS -786T>C polymorphism, but not 894G>T and 4a4b, influences plasma Hcy concentrations mildly but significantly and independently.
The following articles in journals at HighWire Press have cited this article:
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  K. Meyer, A. Fredriksen, and P. M. Ueland MALDI-TOF MS Genotyping of Polymorphisms Related to 1-Carbon Metabolism Using Common and Mass-Modified Terminators Clin. Chem., January 1, 2009; 55(1): 139 - 149. [Abstract] [Full Text] [PDF]
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 C. J. Glueck, R. A. Freiberg, J. Oghene, R. N. Fontaine, and P. Wang Association Between the T-786C eNOS Polymorphism and Idiopathic Osteonecrosis of the Head of the Femur J. Bone Joint Surg. Am., November 1, 2007; 89(11): 2460 - 2468. [Abstract] [Full Text] [PDF]
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 C. J. Glueck, M. Haque, M. Winarska, S. Dharashivkar, R. N. Fontaine, B. Zhu, and P. Wang Stromelysin-1 5A/6A and eNOS T-786C Polymorphisms, MTHFR C677T and A1298C Mutations, and Cigarette-Cannabis Smoking: A Pilot, Hypothesis-Generating Study of Gene-Environment Pathophysiological Associations With Buerger's Disease Clinical and Applied Thrombosis/Hemostasis, October 1, 2006; 12(4): 427 - 439. [Abstract] [PDF]
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