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

Abstract

Background and aimMany 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.MethodsA 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.ResultsFifty-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.ConclusionThe 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.

Role of Gene Polymorphisms/Haplotypes and Plasma Level of TGF-β1 in Susceptibility to In-Stent Restenosis Following Coronary Implantation of Bare Metal Stent in Chinese Han Patients

“…In accordance with our result, Zeng et al 34) failed to confirm that the genetic variation in TGF-β1 is a risk factor for developing ISR after coronary DES implantation in the Chinese Han population. These negative results might be owing to a small sample size, which might not have sufficient statistical power to detect a slight effect of this variation.…”

“…Current studies have examined the relationship between TGF-β1 polymorphisms and ISR. [32][33][34] However, none of the TGF-β1 genetic variations has ever been studied in relation to the risk of ISR after BMS implantation in the Chinese Han population. In the present study, we observed that Cdominant CC/CT genotype frequency of TGF-β1 869T/C polymorphism T869C (rs1800470; Leu10/Pro10; T29C, codon10) is significantly higher in the ISR group after coronary implantation of BMS among Chinese Han patients.…”

“…However, there are limited data assessing the impact of these variants on ISR. [32][33][34] Additionally, whether the genetic variations in TGF-β1 are associated with the risk of ISR after coronary implantation of bare metal stent (BMS) among Chinese Han patients has not been studied.…”

Does the Nitric Oxide Synthase T786C Gene Polymorphism Influence Arterial Stiffness in Patients with Metabolic Syndrome?

“…An enzyme constitutively expressed mainly in endothelial cells, Endothelial Nitric Oxide Synthase (eNOS or NOS3), is responsible for Nitric Oxide (NO) bioavailability at endothelial level. Alterations in endothelial-derived NO production occurs in various cardiovascular diseases (coronary artery disease, myocardial infarction, hypertension, pre-eclampsia, stroke, metabolic syndrome and diabetes [1][2][3][4][5][6][7][8][9][10][11], associated with different polymorphisms in the eNOS gene -one of the most studied being represented by -786T/C (rs2070744) [1][2][3][4][5][6][7][8][9][10][11]. Even in relatively healthy people who are at low risk for cardiovascular disease, arterial stiffness increases with advancing age [12].…”

Research Article Atherosclerosis: analysis of the eNOS (T786C) gene polymorphism.

“…Among the many polymorphisms reported regarding the eNOS gene, two polymorphisms, namely Glu298Asp (G:T) located within exon 7 and T-786C within the promoter, have received much interest in the possible association between such polymorphisms and CAD (Zeng et al, 2017), and the latter has been more intensely investigated (Miyamoto et al, 2000;Nakayama et al, 2000). It involves a cytosine (C) substitution of the thymine nucleotide (T) at the 786 locus of the eNOS gene and is associated with increased susceptibility to coronary vasospasm in homozygotes (C/C) and heterozygotes (T/C), that is individuals expressing the mutant allele (C allele) (Lüscher and Noll, 1999;Nakayama et al, 1999).…”