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

PLoS One. 2017 Jan 27;12(1):e0170964. doi: 10.1371/journal.pone.0170964. eCollection 2017.

Abstract

Background and aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Adult
  • Aged
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / pathology
  • Coronary Artery Disease / surgery
  • Coronary Restenosis / genetics*
  • Coronary Restenosis / pathology
  • Coronary Restenosis / surgery
  • Drug-Eluting Stents / adverse effects*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide Synthase / genetics*
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Stents / adverse effects

Substances

  • Nitric Oxide Synthase

Grants and funding

This work is supported by grants from Health Bureau of Zhejiang Province (2014KYB002) (Wen-ping Zeng), http://www.zjwst.gov.cn/. Author Contribution of WPZ: preparation of the manuscript, data analysis and funding acquisition.