Polymorphism of the gene eNOS G894T (Glu298Asp) in symptomatic patients with aterosclerosis

Abstract

ABSTRACT. Atherosclerotic and its cardiovascular complications are responsible for 17.5 million deaths a year, according to the World Health Organization. There is consensus that atherosclerosis involves multiple pathogenic processes initiated by endothelial dysfunction, with inflammation and vascular proliferation determining alterations in the matrix, with consequent formation of the atheromatous plaque and its clinical implications. Risk factors such as hypertension, diabetes mellitus, dyslipidemia, and smoking are widely known. Currently, genotyping, which is not directly related to these factors, is not accepted to estimate the risk of cardiovascular diseases, but strong evidence indicates several polymorphic genes as factors of risk and progression leading to complications of the disease. Among the genes involved, eNOS (endothelial nitric oxide synthase gene), which is responsible for the production of endothelial nitric oxide (an important arterial vasodilator), when presented in polymorphic variation can determine production, malfunction, and predisposition to atherosclerosis. In the present study, we analyzed the G894T polymorphism of the eNOS gene in groups of individuals diagnosed with atherosclerosis and in a control group. We collected 200 blood samples from patients previously diagnosed with atherosclerosis and 100 samples formed the control group. The genotyping analysis for polymorphism of the eNOS gene was determined by PCR. We considered variables such as gender, smoking, smoking history, and alcohol consumption; statistical differences were found in the distribution of case and control groups (P = 0.0378) and in non-smoking patients (P = 0.0263). In the other associations, no statistically significant difference was found. In the population studied, the frequency of the heterozygous genotype (GT) was much higher than in the other populations (GG and TT) in both groups (case and control). The GG genotype showed greater susceptibility to atherosclerosis. Association of the GG genotype in non-smokers also showed greater susceptibility. Gender, alcohol consumption, smoking, and smoking history did not influence atherosclerosis.

Therapeutic Design of Peptide Modulators of the Interaction Between eNOS and p53 in Atherosclerosis

“…NO produced by the activity of eNOS modulate, beyond other functions, the degree of constriction experienced by a blood vessel, cell cycle progression, senescence or apoptosis, immune system cells activity and platelet aggregation [51][52][53][54][55]. Moreover, availability of NO influences cancer, genomic stability and cardiovascular diseases [31,39,56,57]. Regarding the p53 protein, which is coded by the TP53 gene, is known as the guardian of the genome.…”

“…The eNOS gene regulates the levels of nitric oxide, which is vital for several intracellular biological functions, such as vasodilation, vascular homeostasis, protection of arteries against injuries, cellular growth, signaling pathways and immune response among others [32][33][34][35][36][37]. The eNOS gene has been investigated as a possible biomarker for non-invasive diagnostic and more efficient treatment of cardiovascular diseases [31,[38][39][40].…”

Association Between Endothelial Nitric Oxide Synthase Polymorphisms T786C and G894T and Ischaemic Stroke

“…Kumar et al suggest that eNOS G894T is an important risk factor for IS, specially for LAAS in IS in the North Indian population (24). Furthermore, Campedelli reported that the GG genotype is associated with greater susceptibility to atherosclerosis (30). Moreover, Abdel-Aziz et al recently reported that the TT genotype of eNOS Glu298Asp is an independent risk factor for premature coronary artery disease in Egyptians (31).…”

Association of AGT, ACE, NOS3, TNF, MMP9, CYBA polymorphism with subclinical arterial wall changes

“…TT и GT генотипы были ассоциированы с риском ИБС [36,37] и АГ [38]. Результаты нашего исследования согласуются с исследованием Campedelli с соавт., где наличие GG-генотипа повышало предрасположенность к атеросклерозу [39].…”