The functional consequence of the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene in young healthy volunteers.
OBJECTIVE
To assess the role of the endothelial nitric oxide synthase (eNOS) gene variant as a risk factor for atherosclerosis we sought to investigate whether the Glu298Asp polymorphism of the eNOS gene is associated with functional changes in the endothelium in healthy volunteers.


METHODS
Endothelial function was assessed in 68 normal volunteers (ages 18-44 years) by bilateral forearm venous occlusion plethysmography with intraarterial infusions of increasing doses of acetylcholine for endothelial-dependent vasodilation and, with sodium nitroprusside and verapamil for endothelial-independent vasodilation. Blood was genotyped by polymerase chain reaction and BanII digestion.


RESULTS
Asp homozygotes (TT) had a decreased vasodilatory response to acetylcholine [forearm blood flow (FBF) ratio between infused and control arm, 2.82 +/- 1.10] when compared to GG variant (FBF ratio to acetylcholine, 3.97 +/- 1.90, p= 0.04) and to a certain extent, the GT variant (FBF ratio to acetylcholine, 3.79 +/- 2.28, p= 0.07). There was no effect of eNOS genotype on the response to the endothelial-independent vasodilators-sodium nitroprusside and verapamil.


CONCLUSIONS
Our data show that carriage of the Asp298 variant of the eNOS gene is associated with a blunted endothelial-dependent vasodilation in healthy volunteers. These findings support a genetically determined modulation of endothelial dysfunction, a phenotype of early atherosclerosis in humans.
Godfrey
Valerie
V
Division of Medicine & Therapeutics, University of Dundee, Dundee, UK. v.godfrey@dundee.ac.uk
Chan
Sue-Lyn
SL
Cassidy
Andrew
A
Butler
Robert
R
Choy
AnnaMaria
A
Fardon
Tom
T
Struthers
Allan
A
Lang
Chim
C
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001783:Blood Flow Velocity / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005542:Forearm / Q000098:blood supply; D005838:Genotype; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D010991:Plethysmography / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D014700:Verapamil; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine