title: The T-786C and Glu298Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of Caucasian hypertensive patients.
abstract: 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Clinica Medica 4 University Hospital, University of Padua, via Giustiniani 2, 35126 Padua, Italy. gianpaolo.rossi@unipd.it
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossi
authors.forename: Stefano
authors.initials: S
authors.lastname: Taddei
authors.forename: Agostino
authors.initials: A
authors.lastname: Virdis
authors.forename: Martina
authors.initials: M
authors.lastname: Cavallin
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghiadoni
authors.forename: Stefania
authors.initials: S
authors.lastname: Favilla
authors.forename: Daniele
authors.initials: D
authors.lastname: Versari
authors.forename: Isabella
authors.initials: I
authors.lastname: Sudano
authors.forename: Achille C
authors.initials: AC
authors.lastname: Pessina
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvetti
mesh_terms: 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*
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase