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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Cruz-González
Ignacio
I
Cardiology Department, University Hospital of Salamanca, Salamanca, Spain. cruzgonzalez.ignacio@gmail.com
Corral
Esther
E
Sánchez-Ledesma
María
M
Sánchez-Rodríguez
Angel
A
Martín-Luengo
Cándido
C
González-Sarmiento
Rogelio
R
D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D016022:Case-Control Studies; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018570:Risk Assessment
D000959:Antihypertensive Agents; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III