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The endothelial nitric oxide synthase (Glu298Asp and –786T>C) gene polymorphisms are associated with coronary in-stent restenosis

A.H. Gomma , M.A. Elrayess , C.J. Knight , E. Hawe , K.M. Fox , S.E. Humphries
DOI: http://dx.doi.org/10.1053/euhj.2002.3400 1955-1962 First published online: 2 December 2002

Abstract

Aims Coronary stent deployment is a major advance in percutaneous treatment of ischaemic heart disease, but 10–40% of patients still develop angiographic restenosis by 6 months due to neointimal hyperplasia. Patient-specific factors, including genetic factors, can contribute to this process. We have conducted a prospective study to examine the involvement of genetic risk factors (eNOS, ACE, MMP-3, IL-6, and PECAM-1) in restenosis following coronary stent deployment.

Methods and Results A total of 226 patients who underwent elective and successful coronary artery stenting to de novo lesions in native coronary arteries were studied. Two hundred and five (90·7%) patients were restudied by coronary angiogram at 6 months and the stented lesions were assessed using an automated quantitative angiography system. Genotype was determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Restenosis rate, defined as ≥50% diameter stenosis, was 29·3%. The overall genotype frequency distributions were in Hardy–Weinberg equilibrium for all variants. Carriers of the 298Asp allele of the eNOS Glu298Asp polymorphism showed a higher frequency of restenosis with an odds ratio of 1·88 (95%CI: 1·01–3·51, P=0·043) compared to 298Glu homozygotes. Carriers of the –786C allele of the eNOS –786T>C polymorphism also showed a higher frequency of restenosis with odds ratio of 2·06 (95%CI: 1·08–3·94, P=0·028). These effects were essentially additive and were independent of other classical risk factors. Other studied genes did not show significant association with coronary in-stent restenosis.

Conclusion In patients with coronary artery disease, the possession of the 298Asp and –786C variants of the eNOS gene are a risk factor for coronary in-stent restenosis, demonstrating the importance of the nitric oxide system in restenosis. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.

  • eNOS polymorphism, restenosis, stents, genes, angiography.