eNOS Glu298Asp Polymorphism and Endothelial Dysfunction in Patients with and without End-stage Renal Disease

Abstract

Background: Chronic kidney diseases are known to influence nitric oxide metabolites (NOx) and asymmetric dimethylarginine (ADMA), though the exact mechanism is still poorly understood. Aims: The purpose of the present study was to examine eNOS Glu298Asp gene polymorphism, plasma NOx and ADMA concentration in subjects with and without End-stage Renal Disease. Study Design: Case-control study. Methods: In this study, genotype distributions of Glu298Asp in exon 7 of the eNOS gene polymorphisms in 130 hemodialysis and 64 peritoneal dialysis patients were compared with 92 controls. NOx was measured by using the Griess reaction while arginine, ADMA and SDMA measurements were performed by HPLC. Genotyping for eNOS Glu298Asp polymorphism was detected with the polymerase chain reaction and/or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: When the genotype frequencies of TT and GT genes were compared between both groups, there was no detected statistically important difference, eventhough a TT genotype frequency was 27 (20.8%) versus 17 (26.6%), GT heterozygote genotype frequency was 52 (40%) versus 22 (34.4%), and GG homozygote genotype frequency was 51 (39.2%) versus 25 (39.1%), respectively (p>0.05). NOx, SDMA and ADMA concentrations were significantly elevated in subjects with hemodialysis patients as compared to their corresponding controls. Whereas nitrite was found to be significantly decreased in the patient with peritoneal dialysis. Conclusion: Not observed any connection between the Glu298Asp polymorphism in the eNOS gene and end-stage Renal Diseases in our study population under different dialysis treatments. However, higher ADMA and SDMA concentrations in subjects with ESRD support the existing hypothesis that NOx overproduction affects endothelial dysfunction. Thus, the reduction of ADMA and SDMA concentrations might play a protective role in ESRD patients. Keywords: eNOS Glu298Asp, endothelial dysfunction, end-stage renal disease Endothelial dysfunction and impaired regulation of nitric oxide (NO) system has emerged as the characteristics of chronic kidney diseases (CKD). The accumulation of asymmetric dimethylarginine (ADMA) plays a role in the impairment regulation of NO in these patients; however, the mechanism of these disorders is not clear. Increased levels of ADMA and NO bioavailability reduction play a vital role in the pathogenesis of many diseases like coronary atherosclerosis, CKD or diabetes mellitus (1). Morever, accumulation of reactive oxygen species by the increasing NO leads to atherogenesis, hence a over production may also damage cells and tissues (2).Oxidative stress has a very considerable role in the endothelial dysfunction, vascular damage and in the development of cardiovascular diseases. Some of these mechanisms are associated with the oxidative inactivation of NO production and the inhibition of NO synthase activity by free oxygen radicals

Association of eNOS and ACE gene polymorphisms as a genetic risk factor in gestational diabetes in Iranian women

“…We aimed to evaluate the association of eNOS Glu298Asp and ACE I/D gene polymorphism with GDM in Iranian GDM women. Several studies have been conducted to investigate the relationship between eNOS gene polymorphism and multiple diseases; Ilhan N et al did not observe any association between the Glu298Asp polymorphism in the eNOS gene and end-stage Renal Diseases [17]. Martinelli NC et al showed that the -786C/4b/Asp298 eNOS haplotype had a significant impact on heart failure susceptibility and prognosis, particularly in African-Brazilian patients [18].…”

Role of T-786c Endothelial Gene Polymorphism of No - Synthase in the Development of Acute Contrast-Induced Nephropathy in Patients With Coronary Heart Disease

“…In contrast to the above data, Ilhan N. et al (2016) [19] studied the Glu298Asp eNOS gene polymorphism and endothelial dysfunction in the patients with and without end-stage RF (ESRF) and did not reveal any interdependence between the Glu298Asp eNOS gene polymorphism and ESRF in the group of patients under examination. In the work of Marson B.P.…”