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International Journal of Hypertension
Volume 2010, Article ID 865031, 7 pages
Research Article

An NOS3 Haplotype Is Protective against Hypertension in a Caucasian Population

1Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, 800 Washington Street, Tufts MC no. 63, Boston, MA 02111, USA
2Department of Biomathematics, University of Thessaly School of Medicine, 2 Panepistimiou, Biopolis, Larissa 41100, Greece

Received 4 December 2009; Accepted 13 February 2010

Academic Editor: Tomohiro Katsuya

Copyright © 2010 Georgios D. Kitsios and Elias Zintzaras. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The endothelial nitric oxide synthase gene (NOS3) has been implicated in the development of hypertension, although the specific role of variants and haplotypes has not been clarified. In this study, the association of three polymorphisms (promoter T786C, intronic 4a/b, and nonsynonymous G894T) was tested in a case-control sample of 230 patients with essential hypertension and 306 healthy controls. Haplotype analysis was also performed. The mutant allele a of the 4a/b polymorphism showed a protective effect against hypertension under a dominant model (odds r a t i o = 0 . 6 4 , 95% confidence interval (0.44–0.93)), although this effect was not significant after the adjustment for covariates ( 𝑃 = 0 . 0 6 ). The estimated frequency of the haplotype composed of the T 7 8 6 , 4 a , and G 8 9 4 alleles was significantly higher in controls (5.5%) compared to cases (2%). These results indicate that although individual NOS3 polymorphisms are not associated with hypertension, a rare haplotype of the gene might be protective against the development of hypertension.