<b><i>NOS3</i></b> Gene rs1799983 and rs2070744 Polymorphisms in Patients with Unstable Angina

Abstract

Acute coronary syndrome occurs when the heart muscle does not receive adequate oxygen and nutrients in a timely manner. Acute coronary syndromes are primarily due to atherosclerosis of the coronary arteries, i.e., coronary heart disease. Nitric oxide (NO) is synthesised from L-arginine in endothelial cells by the constitutive calcium-calmodulindependent enzyme, nitric oxide synthase (NOS), which mediates endothelium-dependent vasodilatation. Endothelial nitric oxide synthase (eNOS) is predominantly expressed in endothelial cells. Three NOS isoforms have been detected in different tissue: (1) neuronal NOS (nNOS) (NOS1), (2) eNOS (NOS2), and (3) inducible NOS (iNOS) (NOS3). These isoforms are encoded by three different genes. NOS3 is located on chromosome 7q35-36 and contains 26 exons. Previous studies have suggested that NOS3 polymorphisms may be associated with acute coronary syndromes. Therefore, the aim of the study was to examine the associations between NOS3 rs1799983 (894G/T) and rs2070744 (-786T/C) polymor-phisms and unstable angina. This study included 246 patients with unstable angina, as confirmed by coronary angiography. We also included 189 healthy controls who were also assessed by this technique. There were no significant differences in genotype distributions of NOS3 rs1799983 and rs2070744 polymorphisms in patients with unstable angina and healthy controls in both univariate and multivariate analyses. In patients with the NOS3 rs1799983 TT genotype, we observed a higher BMI (TT vs. GT + GG, p = 0.068), and in patients with the NOS3 rs2070744 TT genotype, we observed a higher waist circumference (TT vs. TC + CC, p = 0.023; TT vs. CC, p = 0.0053). These data suggest a lack of association between the NOS3 rs1799983 and rs2070744 polymorphisms and unstable angina in our patient population. However, these polymorphisms may be associated with some obesity parameters, rs1799983 in females and rs2070744 in males.

Antioxidants-Related Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX), Glutathione-S-Transferase (GST), and Nitric Oxide Synthase (NOS) Gene Variants Analysis in an Obese Population: A Preliminary Case-Control Study

“…Nasr et al also observed a significant association of rs1799983*T allele with obesity and BMI in the Tunisian population [42]. Additionally, recently, Pawlik et al reported a significant association of this variant with BMI and waist circumference in female patients with unstable angina [43]. Although in some studies, including ours, the rs1799983*G allele was more prevalent in the obese cohort than controls that differs from other studies in which the rs1799983*T allele was the risky one, previous reports have indicated interethnic differences in rs1799983 distribution and evidence for linkage disequilibrium with other SNPs exists among populations [86,87].…”

“…These three isozymes can impact obesity etiology through NO production that plays essential roles in regulating adiposity, energy expenditure, and insulin sensitivity [39,40]. The NOS2 rs2297518 [A/G] and NOS3 rs1799983 [G/T] genetic variations were associated with insulin resistance, obesity, and/or a higher BMI in several populations [41][42][43].…”

Potential Role of eNOS Genetic Variants in Ischemic Heart Disease Susceptibility and Clinical Presentation

“…However, results regarding the association between eNOS genetic variants and IHD susceptibility and clinical presentation are often conflicting or inconclusive [ 20 ]. In this context, Pawlik et al demonstrated that there is no association among the NOS3 rs1799983 and rs2070744 polymorphisms and unstable angina [ 32 ]. Additionally, Vargan-Alarcon et al found no differences regarding the eNOS polymorphism distribution between patients with ACS and healthy control groups [ 33 ].…”

“…The interaction among the eNOS gene and other genes, as well as gene–environment interaction, may have an impact on polymorphism function [ 18 ]. In this context, several studies have shown an association between the eNOS rs1799983 polymorphism and IHD in different populations, although in some cases, this association has not been demonstrated, probably due to interethnic differences [ 32 ]. For this reason, significant results on larger and new cohorts of patients are needed to validate new genetic predictors of IHD and ACS.…”

A meta-analysis of the effects of endothelial nitric oxide synthase 4ba polymorphism on renal interstitial fibrosis in diabetic nephropathy

“…DN is one of the most serious complications in diabetic patients and one of the main causes of death (1). As a leading cause of end-stage renal disease, second only to glomerulonephritis, DN is often accompanied by complications such as chronic hyperglycemia and proteinuria (2,3).…”