The T-786C and Glu298Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of Caucasian hypertensive patients.
OBJECTIVE
We sought to investigate whether two polymorphisms located in the promoter (T(-786)C) and exon 7 (Glu298Asp) of the endothelial nitric oxide (NO) synthase (eNOS) gene affected agonists-mediated NO release.


BACKGROUND
Endothelial dysfunction can be genetically determined. Therefore, we investigated whether two polymorphisms located in the eNOS gene affected agonists-mediated NO release.


METHODS
We compared endothelial-dependent and -independent vasodilation of the different eNOS genotypes in a cross-sectional study on 187 subjects, of whom 137 were uncomplicated essential hypertensive patients (PH) (49 +/- 9 years, 151 +/- 11/99 +/- 5 mm Hg) and 50 healthy normotensive subjects (NT) (43 +/- 16 years, 123 +/- 10/78 +/- 7 mm Hg). Endothelial-dependent and -independent vasodilation was assessed as the forearm blood flow response to incrementally increasing doses of acetylcholine (0.15, 0.45, 1.5, 4.5, 15 microg/100 ml/min) and sodium nitroprusside (1, 2, 4 microg/100 ml/min), respectively. Genotyping was performed with melting curve analysis (Lightcycler) of polymerase chain reaction products from acceptor (5' end-labeled with LCRed 640) and donor probes (3' end-labeled with fluorescein) specific for each polymorphism. The genotype distribution of T(-786)C (CC = 21.9%, CT = 48.7%, TT = 29.4%) and Glu298Asp (GG = 39.0%, GT =51.9%, TT = 9.1%) was similar in PH and NT. A repeated measure analysis of variance showed a blunting of endothelium-dependent vasodilation in PH compared with NT (p < 0.001). A significant effect of the T(-786)C (p = 0.002) but not of the Glu298Asp (p = NS) eNOS polymorphism on endothelial-dependent vasodilation was found. However, we also detected a significant interaction between the T(-786)C and Glu298Asp polymorphism (p < 0.001). No effect on either polymorphism on endothelial-independent vasodilation was seen.


CONCLUSIONS
The T(-786)C promoter polymorphism and its interaction with exon 7 Glu298Asp affect endothelium-dependent vasodilation in mild-to-moderate PH patients and NT Caucasian subjects.
Rossi
Gian Paolo
GP
Department of Clinical and Experimental Medicine, Clinica Medica 4 University Hospital, University of Padua, via Giustiniani 2, 35126 Padua, Italy. gianpaolo.rossi@unipd.it
Taddei
Stefano
S
Virdis
Agostino
A
Cavallin
Martina
M
Ghiadoni
Lorenzo
L
Favilla
Stefania
S
Versari
Daniele
D
Sudano
Isabella
I
Pessina
Achille C
AC
Salvetti
Antonio
A
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D005091:Exons / Q000235:genetics*; D005260:Female; D005542:Forearm / Q000098:blood supply* / Q000503:physiopathology*; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000235:genetics* / Q000502:physiology*; D014664:Vasodilation / Q000235:genetics* / Q000502:physiology*; D044465:White People / Q000235:genetics*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase