Research Article: Association of the Endothelial Nitric Oxide Synthase Gene T786C Polymorphism with In-Stent Restenosis in Chinese Han Patients with Coronary Artery Disease Treated with Drug-Eluting Stent

Date Published: January 27, 2017

Publisher: Public Library of Science

Author(s): Wen-ping Zeng, Rui Zhang, Ran Li, Jin-fang Luo, Xiao-feng Hu, Joseph Devaney.


Many studies have reported that genetic variants correlate with higher risk for coronary artery disease (CAD) or in-stent restenosis (ISR) after bare metal stent (BMS) implantation. However, there is limited data assessing the impact of these variants on ISR in patients treated with drug-eluting stent (DES). The purpose of this study was to investigate the effects of genetic risk factors on ISR in Chinese Han patients treated with DES.

A total of 425 patients with a diagnosis of CAD who underwent successful revascularization in native coronary arteries with DES were included in this retrospective study. Genotyping was performed on six single nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase gene (eNOS), the angiotensin converting enzyme gene (ACE), the angiotensin II type 1 receptor gene (AT1R), the transforming growth factor beta gene (TGF-β), and the vascular endothelial growth factor gene (VEGF). Quantitative coronary angiography (QCA) was performed during the follow-up period to detect ISR. Logistic regression models were used to test for association.

Fifty-four patients (12.7%) developed ISR during the follow-up period. Of the six analyzed SNPs, the frequency of the C allele of T786C polymorphism in eNOS was significantly higher in the ISR group (22.2%) compared to the non-ISR group (12.7%) (p<0.01). In the ISR group, the frequency of the TT, TC, and CC genotypes was 61.1%, 33.3%, and 5.6%, respectively, and in the non-ISR group, the frequencies were 76.8%, 21.0%, and 2.2%, respectively. The multivariable analysis adjusted for potential confounders and revealed that the T786C polymorphism increased the risk of ISR in both additive and dominant models with odds ratios of 1.870 (95% confidence interval [CI]: 1.079–3.240, p = 0.03) and 2.045 (95% CI: 1.056–3.958, p = 0.03), respectively. The eNOS T786C polymorphism was associated with ISR in Chinese Han patients treated with DES. Genotyping may be helpful to identify patients with higher risks of ISR after DES implantation.

Partial Text

Cardiovascular diseases, particularly coronary artery disease (CAD), remain the leading cause of mortality worldwide. Percutaneous coronary intervention is widely used for the treatment of coronary artery disease and results in better outcomes than balloon angioplasty alone [1]. However, after a successful intervention, in-stent restenosis (ISR) can develop, leading to the recurrence of myocardial ischemia symptoms that are not completely relieved by drug-eluting stents (DES) [2–4]. Thus, development of ISR in patients undergoing percutaneous coronary intervention (PCI) with DES remains a critical problem limiting successful treatment.

In this study, we investigated the association of six common genetic variants with the risk of ISR after DES implantation. We demonstrated that the C allele of the eNOS T786C polymorphism was linked with an increased risk of ISR in Chinese patients treated with DES. Multivariate analysis showed that this association was independent of other traditional risk factors of ISR.