eNOS Gene Variants and the Risk of Premature Myocardial Infarction

Abstract

BACKGROUND: Endothelial nitric oxide synthase (eNOS) as well as nitric oxide play an important role in the regulation of cardiovascular function. There are limited and controversial data regarding the impact of polymorphisms of eNOS gene that is implicated in the vasoconstrictive properties of the endothelium in the pathogenesis of premature myocardial infarction (MI).OBJECTIVE: We examined whether two common polymorphisms of eNOS gene (G894T and T786C) are associated with the development of premature MI.METHODS: We recruited 107 patients with premature MI and compared them to 103 age- and sex- matched controls. All patients underwent coronary angiogram and were classified into the subgroup of patients with ‘normal’ or ‘near normal’ coronary arteries and the subgroup of patients with significant coronary artery disease (≥ 50% stenosis in lumen diameter of coronary arteries). The genetic polymorphisms of eNOS gene were assayed with polymerase chain reaction and reverse hybridization.RESULTS: Nineteen patients (17.8%) had ‘normal’ or ‘near normal’ coronary arteries. A significantly higher frequency of homozygosity for the 786C (32%) and the 894T (21%) alleles of the eNOS gene in patients who develop early MI in the setting of angiographically 'normal' or 'near normal' coronary arteries were found.CONCLUSIONS: Our data suggest that the T786C and the G894T genetic polymorphisms are associated with the development of MI in very young individuals, whose coronary arteries are characterized by very small atheromatic burden.

Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms with Coronary Artery Disease: An Updated Meta-Analysis and Systematic Review

“…Among subgroups for Glu298Asp, 17 studies belonged to the European, [2] , [3] , [5] , [15] , [18] , [20] , [21] , [28] , [32] , [37] – [39] , [53] – [65] 14 to the Middle Eastern, [14] , [16] , [23] , [66] – [76] 10 to the Asian, [10] , [11] , [22] , [77] – [83] 8 to the Asian-Indian [13] , [84] – [90] and 1 to the African [57] group. ( Tables 1 and 2 ) The Asian-Indian subgroup in all its genetic models showed low heterogeneity ( I 2 range = 18–23% and P Q range = 0.26–0.28).…”

“…Twenty nine case-control studies [5] , [17] , [22] , [23] , [27] , [28] , [31] , [32] , [37] , [39] , [54] , [55] , [57] , [58] , [62] , [64] , [65] , [76] , [79] , [82] , [89] – [97] with 7,043 CAD patients and 10,409 controls, investigating the association between T786-C polymorphism and CAD were included in the pooled analysis. ( Tables 1 and 2 ) Moderate heterogeneity was seen across all genetic models ( I 2 range = 35–69%, P Q range = 0.03 to <0.00001).…”

“…Among the ancestral subgroups, 15 studies constituted the European group, [5] , [27] , [28] , [32] , [37] , [39] , [54] , [55] , [58] , [62] , [64] , [65] , [91] – [93] while 5,6,2 and 1 study respectively constituted Middle Eastern, [17] , [23] , [76] , [94] , [95] Asian, [22] , [31] , [79] , [82] , [96] , [97] Asian-Indian [89] , [90] and African [57] group. ( Tables 1 and 2 ) Moderate to high degree of heterogeneity was seen in almost all ancestral groups (except Africans, which had only 1 study), and in amongst almost all comparisons, barring the recessive model amongst the Asians which was rather homogenous ( I 2 range = 50–72%, P Q range = 0.16 to <0.00001).…”

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

“…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] . However, previous clinical studies were tackled SNP in eNOs gene with endogenous NO production and vascular endothelial growth factor (VEGF), which is reported as key regulator of angiogenesis, coagulation and tissue reparation [35,36] .…”

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

“…Because altered NO bioavailability in patients with 786CC polymorphism in eNOs gene can cause endothelial cell dysfunction, restenosis and early thrombosis of the stent 33,34 , we received a clinical confirmation regarding the independent negative impact of 786CC polymorphism in eNOs gene on MACE and hospital admission after STEMI over 6 months after completed reperfusion. Additionally, this finding can be important for acute STEMI patients with angiographically normal large coronary arteries, because there was evidence that 786CC polymorphism was associated with acute myocardial infarction, especially without severe coronary organic stenosis [35][36][37] . However, a risk of STEMI-related complications can sufficiently increase in individuals with 786CC polymorphism 38,39 .…”