The Endothelial Nitric Oxide Synthase Gene T-786C Polymorphism Increases Myocardial Infarction Risk: A Meta-Analysis

Abstract

BackgroundPolymorphisms of the endothelial nitric oxide synthase (eNOS) gene are reportedly associated with myocardial infarction (MI) risk. However, definitive evidence of this association is lacking. In this study, we investigated the potential association of eNOS gene polymorphisms with MI risk by conducting a meta-analysis of studies evaluating this association.Material/MethodsPubMed, Web of Knowledge, ScienceDirect, China National Knowledge Infrastructure (CNKI), WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP) were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated to evaluate the association of eNOS gene T-786C and 4b4a polymorphisms with MI risk.ResultsFifteen studies with 8,067 controls and 4,923 MI cases were included in the final meta-analysis. In the overall analysis, T-786C (rs2070744) polymorphism was associated with MI risk (p<0.05, OR=1.69, 95% CI: 1.53–1.86 for T vs. C; p<0.05, OR=2.76, 95% CI: 2.03–3.75 for TT vs. CC; p<0.05, OR=1.74, 95% CI 1.56–1.95 for TT vs. (CT + CC); p<0.05, OR=2.43, 95% CI: 1.79–3.30 for (CT + TT) vs. CC). In addition, a significant association between 4b4a VNTR polymorphism and MI risk was observed. On sub-group analyses by ethnicity, a significant increase in MI risk was observed separately for Asian and Caucasian populations for T-786C polymorphism, but not for the 4b4a polymorphism.ConclusionsIn this meta-analysis, T-786C polymorphism of the eNOS gene was associated with the risk of MI, especially in the Asian populations.

Multilocus Analysis of Genetic Susceptibility to Myocardial Infarction in Russians: Replication Study

“…The C allele associated with the risk of MI in our study is related to downregulation of mRNA expression and, correspondingly, the eNOS protein level [40]. Our data are consistent with the findings reported in other publications [41].…”

Biomarker-based Prognostication of Adverse Cardiac Remodeling after STEMI: the Role of Single Nucleotide Polymorphism T786C in Endothelial NO-synthase gene

“…Yet, SNP in promoter region of eNOs gene was strongly associated with a risk of cardiovascular and renal disease in several populations [28,29] . Moreover, meta-analysis provided by Kong XZ et al (2017) [30] is reported that 786СС polymorphism in eNOs gene corresponded well with increased risk of primary MI. Therefore, negative impact of the 786СС polymorphism in eNOs gene on a risk of death after MI was determined in manyfore populations [31][32][33][34] .…”

“…Previous preclinical and clinical studies have been shown that genetic deletion of promoter region of eNOs gene -single nucleotide polymorphisms (SNP) T786C -frequently associated with lowered NO production [4] . SNP T786C in eNOs gene corresponded to lipid infiltration of vascular wall, apoptosis of mature and progenitor endothelial cells, oxidative stress-induced microvascular inflammation, mononuclear infiltration, proliferation of vascular smooth muscle cells (VSMCs), accumulation of extracellular matrix components, and platelet aggregation on the surface of endothelium [5][6][7] . Collectively, impaired eNO bioavailability was found as main trigger for endothelial dysfunction, accelerating atherosclerosis, and thrombosis [8] .…”

Short-term clinical outcomes in patients with acute myocardial infarction after successful percutaneous coronary revascularization: the role of promoter polymorphism of the endothelial nitric oxide synthase gene

“…Dyslipidemia and lipids in peripheral blood were not the factors contributing to the impact of 786CC eNOS polymorphism on clinical outcomes, even though T2DM was determined as a predictor. Previous clinical studies have shown that sev-eral comorbidities (T2DM, dyslipidemia, the severity of atherosclerosis, smoking) were reported as cofactors influenced on natural evolution of acute myocardial infarction 13,32 . Early investigations were not confirmed as predictive potency of 786CC in eNOs gene polymorphism in acute STEMI patients 17,18 ,as these studies were performed before the primary PCI era.…”

“…Nitric oxide (NO) is an established factor in maintaining endothelial function and vascular wall integrity [1][2][3][4] . Genetic polymorphisms of endothelial NO synthase (eNOs) is associated with altered NO levels in peripheral blood, increased levels of plasma low-density lipoproteins (LDL) and oxidized lipids, suppressed the production of vascular endothelial growth factor and increased fasting glucose 5-7. These findings were reported to have clinical significance in acute ST-segment elevation myocardial infarction (STEMI), stable coronary artery disease (CAD), asymptomatic atherosclerosis, heart failure (HF), abdominal obesity, hypertension, diabetes mellitus, and restenosis and thrombosis after primary percutaneous coronary artery intervention (PCI) 8-10. Previous studies have shown that polymorphism in promoter region of eNOs gene (T786C) in STEMI patients is corresponding with impaired pleiotropic effect of NO, which led to adverse cardiac remodeling, early stent thrombosis and restenosis after PCI [11][12][13][14] . T786C eNOs genotype can predict cardiovascular (CV) mortality in high-risk patients 15 and individuals with stable CAD 16 , while several studies have reported controversies issues regarding the discriminative values of T786C eNOs genotype in STEMI patients 17,18 .…”