Open Access Highly Accessed Research article

Association between -T786C NOS3 polymorphism and resistant hypertension: a prospective cohort study

Ignacio Cruz-González1*, Esther Corral2, María Sánchez-Ledesma3, Angel Sánchez-Rodríguez3, Cándido Martín-Luengo1 and Rogelio González-Sarmiento24

Author Affiliations

1 Cardiology Department, University Hospital of Salamanca, Salamanca, Spain

2 Molecular Medicine Department, University of Salamanca, Salamanca, Spain

3 Internal Medicine Department, University Hospital of Salamanca, Salamanca, Spain

4 Instituto de Biologia Molecular y Celular del Cancer (IBMCC), BMCC, University of Salamanca- CSIC, Salamanca, Spain

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BMC Cardiovascular Disorders 2009, 9:35  doi:10.1186/1471-2261-9-35

Published: 4 August 2009



It is estimated that 5% of the hypertensive patients are resistant to conventional antihypertensive therapy. Polymorphisms in the endothelial nitric oxide synthase (NOS3) gene have been associated with high blood pressure levels, but not with resistant hypertension. The aim of the present study was to investigate if the -786T>C and G894T (Glu298Asp) polymorphisms of the NOS3 gene were associated with resistant hypertension.


A prospective case-control observational study was performed. From a series of 950 consecutive patients followed up during 42 months, 48 patients with resistant hypertension were detected. 232 patients with controlled high blood pressure were also included.


No differences were observed in the distribution of G894T (Glu298Asp) NOS3 genotypes between the resistant hypertension group and the controlled hypertension patients. However, genotype -786CC was more frequent in the group of patients with resistant hypertension (33.3%) than in the group of patients with controlled high blood pressure (17.7%) (p 0.03). Furthermore carriers of allele T (-786TC and -786TT) were more frequent in patients with controlled hypertension (82.3%) than those with resistant hypertension (66.7%) (Multivariate analysis; RR 2.09; 95% CI 1.03–4.24; p 0.004).


Our results indicate that genotype -786CC of the NOS3 gene increase the susceptibility to suffer resistant hypertension, which suggest that resistance to conventional therapy could be determined at the endothelial level.