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Endothelial function and carotid intima-media thickness in young healthy subjects among endothelial nitric oxide synthase Glu298-->Asp and T-786-->C polymorphisms.

Abstract：

BACKGROUND AND PURPOSE:To assess the role of the endothelial nitric oxide synthase (eNOS) gene variants as risk factors for early atherosclerosis, we sought to investigate whether two polymorphisms located in the exon 7 (Glu298-->Asp) and in the promoter region (T-786-->C) of the eNOS gene were associated with functional changes in the endothelium and carotid intima-media thickness (IMT). METHODS:Endothelium-dependent flow-mediated brachial artery dilation (FMD), endothelium-independent dilation response to glyceryl trinitrate (GTN), and carotid IMT were assessed by high-resolution ultrasound in 118 healthy young nonsmoker subjects (30.1+/-0.5 years) genotyped for the eNOS Glu298-->Asp and T-786-->C polymorphisms. RESULTS:Carotid IMT was inversely related to FMD by univariate analysis (r=-0.28, P=0.002) and after adjustment for possible confounders in all the subjects (P<0.01). Asp homozygotes had a significantly lower FMD than Glu carriers (Glu/Glu: 15.0%+/-1.0%, Glu/Asp: 13.3%+/-0.7%, Asp/Asp: 9.6%+/-1.6%; P=0.005), whereas FMD was unaffected by the T-786-->C variant. Neither the Glu298-->Asp nor the T-786-->C polymorphisms influenced the GTN-mediated dilation. With respect to Glu carriers, Asp/Asp genotype displayed a significantly greater carotid IMT (Glu/Glu: 0.37+/-0.01 mm, Glu/Asp: 0.35+/-0.01 mm, Asp/Asp: 0.45+/-0.03 mm; P=0.0002) and significant correlations between carotid IMT and FMD (r=-0.48, P=0.04) and between carotid IMT and resting brachial artery diameter (r=0.70, P=0.001). No difference in IMT was found across the T-786-->C genotypes. By multivariate regression analysis, Asp/Asp genotype was the only significant and independent predictor of flow-mediated brachial artery dilation (FMD) (P=0.04) and carotid intima-media thickness (IMT) (P=0.006). CONCLUSIONS:The eNOS Glu298-->Asp polymorphism may be related to early atherogenesis.

journal_name

Stroke

journal_title

Stroke

authors

Paradossi U,Ciofini E,Clerico A,Botto N,Biagini A,Colombo MG

doi

10.1161/01.STR.0000126482.86708.37

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

1305-9

issue

eissn

0039-2499

issn

1524-4628

pii

01.STR.0000126482.86708.37

journal_volume

pub_type

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Endothelial function and carotid intima-media thickness in young healthy subjects among endothelial nitric oxide synthase Glu298-->Asp and T-786-->C polymorphisms.