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


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 >or=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.


CONCLUSIONS
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.
Gomma
A H
AH
National Heart and Lung Institute, Royal Brompton Hospital, Imperial College of Science, Technology & Medicine, London, UK.
Elrayess
M A
MA
Knight
C J
CJ
Hawe
E
E
Fox
K M
KM
Humphries
S E
SE
D000704:Analysis of Variance; D002985:Clinical Protocols; D023903:Coronary Restenosis / Q000201:enzymology / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D015607:Stents
D004247:DNA; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III