The Glu298Asp polymorphism in endothelial nitric oxide synthase gene is associated with coronary in-stent restenosis

Reduced or impaired synthesis of nitric oxide promotes the proliferation of vascular smooth muscle cells, and thus may induce the neointimal formation leading to coronary in-stent restenosis. Recent reports have suggested that the Glu298Asp polymorphism in exon 7 of the endothelial nitric oxide synthase gene is associated with coronary spasm and acute myocardial infarction. In this study, we have examined the implication of this polymorphism with regard to coronary restenosis after Palmaz-Schatz stent deployment.

Eighty-nine lesions in 85 consecutive patients were treated with Palmaz-Schatz stents, and were prospectively followed up for 6 months. The lesions were classified into a restenosis group (% diameter stenosis=50%) and a non-restenosis group. Assessment was made using an automated quantitative angiographic system. We performed polymerase chain reaction-restriction fragment length polymorphism analysis to detect the missense Glu298Asp variant in exon 7 of the endothelial nitric oxide synthase gene.

Coronary risk factors and angiographic findings of stenotic lesions did not differ between the groups. Univariate analyses showed that the missense Glu298Asp variant was the only statistically significant predictor of restenosis (odds ratio, 4.27; P=0.025). In addition, multiple logistic regression analysis revealed the missense Glu298Asp variant as the only independent predictor for in-stent restenosis (odds ratio, 3.90; P=0.036).

The missense Glu298Asp variant may be an independent risk factor for in-stent restenosis.