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Polymorphisms of the endothelial nitric oxide synthase (NOS3) gene in preeclampsia: a candidate-gene association study

Nikos Zdoukopoulos12, Chrysa Doxani2, Ioannis E Messinis1*, Ioannis Stefanidis3 and Elias Zintzaras24

Author Affiliations

1 Department of Obstetrics and Gynaecology, University of Thessaly School of Medicine, Larissa, Greece

2 Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece

3 Department of Nephrology, University of Thessaly School of Medicine, Larissa, Greece

4 Center for Clinical Evidence Synthesis, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA

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BMC Pregnancy and Childbirth 2011, 11:89  doi:10.1186/1471-2393-11-89

Published: 3 November 2011



The endothelial nitric oxide synthase gene (NOS3) has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the NOS3 gene in a population of Caucasian origin.


We examined the association of three common variants of the NOS3 gene (4b/a, T-786C and G894T) and their haplotypes in a case-control sample of 102 patients with preeclampsia and 176 women with a history of uncomplicated pregnancies. Genotyping for the NOS3 variants was performed and odds ratios and 95% confidence intervals were obtained to evaluate the association between NOS3 polymorphisms and preeclampsia.


The single locus analysis for the three variants using various genetic models and a model-free approach revealed no significant association in relation to clinical status. The analysis of haplotypes also showed lack of significant association.


Given the limitations of the candidate-gene approach in investigating complex traits, the evidence of our study does not support the major contributory role of these common NOS3 variants in preeclampsia. Future larger studies may help in elucidating the genetics of preeclampsia further.