Key result
The eNOS Asp/Asp genotype was associated with significantly lower flow-mediated dilation (9.6% vs 15.0% in Glu/Glu; P=0.005) and greater carotid intima-media thickness (0.45 mm vs 0.37 mm; P=0.0002).
Why the study?
Are eNOS gene variants (Glu298-->Asp and T-786-->C) associated with functional changes in the endothelium and carotid IMT in healthy young subjects?
Cross-Sectional (n=118)
Are eNOS gene variants (Glu298-->Asp and T-786-->C) associated with functional changes in the endothelium and carotid IMT in healthy young subjects?
Absolute Event Rate: 9.6% vs 15%
p-value: p=0.005
The eNOS Glu298-->Asp polymorphism is associated with impaired endothelial function and increased carotid IMT in young healthy subjects, suggesting a genetic predisposition to early atherogenesis.
May flag early vascular risk in healthy youth; hypothesis-generating for eNOS variants and requires prospective validation.
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.
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Paradossi et al. (2004) conducted a cross-sectional in Healthy young nonsmokers (n=118). eNOS Glu298-->Asp polymorphism (Asp/Asp genotype) vs. Glu carriers (Glu/Glu and Glu/Asp genotypes) was evaluated on Endothelium-dependent flow-mediated brachial artery dilation (FMD) (p=0.005). The eNOS Asp/Asp genotype was associated with significantly lower flow-mediated dilation (9.6% vs 15.0% in Glu/Glu; P=0.005) and greater carotid intima-media thickness (0.45 mm vs 0.37 mm; P=0.0002).
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