eNOS Glu298Asp Gene Polymorphism Research Articles

Low HDL cholesterol and the eNOS Glu298Asp polymorphism are associated with inducible myocardial ischemia in patients with suspected stable coronary artery disease

BackgroundThe endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD).AimTo investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD.MethodsA total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient.ResultsIn the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD.ConclusionIn this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD.

Association of eNOS Glu298Asp polymorphism with cardiometabolic risk and inducible myocardial ischemia in patients with stable coronary artery disease

Abstract Background The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause insulin resistance, hypertension, hypertriglyceridemia and impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphism (Glu298Asp, G894T), able to reduce eNOS activity, was associated either with features of the metabolic syndrome or prevalence of coronary artery disease (CAD). Purpose To investigate the possible association of Glu298Asp polymorphism with cardiometabolic risk [insulin resistance, increased triglycerides (TG) and low HDL-cholesterol (HDL-C)], obstructive CAD and inducible myocardial ischemia in stable patients with suspected coronary disease. Methods Six cardiology units enrolled a total of 506 consecutive patients (314 males; mean age 62±9 years) referred for suspected CAD within the BIOGEN-CARE Tuscan Region Italian Study. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible ischemia and 436 patients underwent non invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD (>50% stenosis in at least one major coronary vessel). Blood samples were collected from each patient for genotyping and measurements of lipid and glucose parameters. The TG/HDL-C ratio and the TyG-index [ln(TG × Fasting plasma glucose/2)] were used as synthetic markers of atherogenic dyslipidemia and insulin resistance, main components of the cardiometabolic risk. Results In the whole population, 49.6% of patients were homozygous for the G894allele, 40.9% heterozygotes, and 9.5% homozygous for T894. Myocardial ischemia was documented in 160/325 (49.2%) patients undergoing stress testing and obstructive CAD in 178/436 (40.8%) patients undergoing coronary angiography. Patients carrying the T allele (dominant model TT+GT vs GG) had higher TG/HDL ratio (2.7±1.8 vs 2.5±1.9, P=0.03) (Figure) without differences in other lipid and glucose markers. Independent predictors of obstructive CAD were age, gender, obesity, diabetes and TG/HDL-C ratio but not the the T allele (OR 0.80; CI 0.51–1.25; ns). Independent predictors of inducible ischemia were age, gender, obesity and the T allele (OR 1.91; CI 01.19–3.08; P=0.007). Stratifying the population for both obstructive CAD and ischemia, the T allele was associated with increased risk of ischemia (OR 1.96; CI 1.11–3.44; P=0.02) even after adjustment for the presence of obstructive CAD (OR 3.09; CI 1.85–5.78; P<0.001) (Figure 1). Conclusions In stable patients with suspected CAD, the eNOS Glu298Asp gene polymorphism is an independent risk factor for inducible myocardial ischemia and is significantly associated with the specific cardiometabolic risk expressed by high TG and low HDL-C which independently predicts obstructive CAD. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): “BIOhumoral and GENetic predictors of CARdiac Evolving phenotype in Ischemic Heart Disease (BIOGENCARE-IHD)”; funded by Toscan Region-Programma per la ricerca regionale in materia di Salute 2009

Endothelial nitric oxide synthase Glu298Asp gene polymorphism in the cases of idiopathic thrombocytopenic purpura.

BackgroundNitric oxide (NO) can induce apoptosis in megakaryocytes. Stimulatory function of NO on platelet production may be important in the pathophysiology of idiopathic thrombocytopenic purpura (ITP). NO is produced by three isoforms of NO synthase (NOS). The endothelial nitric oxide synthase (eNOS) isoform has been detected in platelets. Polymorphism of the eNOS gene, which supplies NO synthesis, changes the functions of this enzyme. In this study, the role of eNOS Glu298Asp gene polymorphism in etiopathogenesis, its course, and treatment of ITP was investigated.MethodsSixty-six patients [51 newly diagnosed ITP (ND-ITP), 15 chronic ITP (CH-ITP), and 60 healthy controls (HC)] were enrolled in this study.ResultsIn all patients, the frequency of the GT genotype was 48.5%. The frequency of the GG genotype was determined to be 40.9% and the TT genotype was 10.6%. The most common allele in all patients was the G allele. eNOS Glu298Asp gene polymorphism might be a risk factor in the etiopathogenesis of ITP. Patients with the GG genotype were thought to have a high intention for CH-ITP. Patients with the GG genotype responded effectively to medical treatment using IVIG therapy. The presence of the G allele was observed to have a positive effect on the medical treatment of patients with CH-ITP, whereas the T allele exhibited a negative effect.ConclusionIn the present study, a significant correlation was found between ITP and eNOS Glu298Asp gene polymorphism. This correlation suggested that eNOS Glu298Asp gene polymorphism might be a risk factor in the ethiopathogenesis of ITP.

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

Chronic kidney diseases are known to influence nitric oxide metabolites (NOx) and asymmetric dimethylarginine (ADMA), though the exact mechanism is still poorly understood. 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. Case-control study. In this study, genotype distributions of Glu-298Asp 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. When the genotype frequencies of TT and GT genes were compared between both groups, there was no detected statistically important difference, even-though 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. 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.

The rates of eNOS Glu298Asp gene polymorphism among psoriatic patients in Çanakkale, Turkey

The rates of eNOS Glu298Asp gene polymorphism among psoriatic patients in Çanakkale, Turkey

The rates of eNOS Glu298Asp gene polymorphism among psoriatic patients in Çanakkale, Turkey

Psoriasis is a complex immunological disease with several comorbidities. Thus several genes related to immun system was recognized as disease susceptibility genes. On the other hand, the conserved mechanism that triggers both psoriasis and comorbidities are important to identify the common physiology of diseases. Thus, in this study, the prevalence and distribution of the eNOS Glu298Asp polymorphism among psoriatic patients were evaluated. 114 psoriatic patients, who gave informed consent, were enrolled in the study. The genotype frequencies for eNOS gene polymorphism were determined by melting curve analyses (Real time PCR). In consistency of genotype frequencies (biallelic markers) with the Hardy-Weinberg equilibrium was tested using a Chi-Square test on a contingency table of observed versus predicted genotype frequencies. Sixty two patients (54.4%) had the genotype Glu/Glu (wild group) and 52 (45.6%) patients a mutant genotype, Glu/Asp (46 patients, 40.4%) or Asp/Asp (6 patients, 5.2%). The genotype distribution were consistent with Hardy-Weinberg equilibrium for psoriatic groups (χ²calculate: 0,496 1st degree). We could not found any differences between allelic distribution or genotype frequency of eNOS Glu298Asp gene polymorphism and psoriasis.

Association of Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism with the Risk of End-Stage Renal Disease

The association between endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphism and end-stage renal disease (ESRD) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS Glu298Asp gene polymorphism and ESRD susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Six articles were identified for the analysis of association between eNOS Glu298Asp gene polymorphism and ESRD risk. T allele was associated with ESRD susceptibility in overall populations and in Asians (overall populations: p = 0.01, Asian: p < 0.00001). Furthermore, GG genotype might play a protective role against ESRD onset for overall populations, Asians, and Africans. However, a link between eNOS Glu298Asp gene polymorphism and ESRD risk was not found in Caucasians and Brazil population. In conclusion, T allele might become a significant genetic molecular marker for the onset of ESRD in overall populations, and in Asians. However, more studies should be performed in the future.

Association between Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism and Diabetic Nephropathy Susceptibility

The association between endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphism and diabetic nephropathy (DN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS Glu298Asp gene polymorphism and DN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Eight articles were identified for the analysis of association between eNOS Glu298Asp gene polymorphism and DN risk. T allele was associated with DN susceptibility in overall populations, in Asians, and for Caucasians (overall populations, p = 0.005; Asians, p = 0.004; Caucasians, p = 0.002). Furthermore, GG genotype might play a protective role against DN onset for overall populations, Asians, Caucasians, and Africans. However, a link between eNOS Glu298Asp gene polymorphism and DN risk was not found in overall populations, Asians, Caucasians, and Brazil population. In conclusion, T allele might become a significant genetic molecular marker for the onset of DN in overall populations, in Asians, and for Caucasians. However, more studies should be performed in the future.

Intergenotypic Variation of Endothelial Dysfunction and Inflammatory Markers in Eclampsia

Background. Cytokine imbalance and endothelial dysfunction are suggested to have a pivotal role in eclampsia. Pathophysiological processes are influenced by genetic factors and nitric oxide (NO) synthases seem to play important roles, although their role is still unclear. Endothelial NO synthase (eNOS) gene polymorphism may affect cytokine production. The aim of this study was to test the hypothesis that inflammatory cytokines impairs endothelium-dependent relaxation and NO production gets vitiated due to eNOs Glu298Asp gene polymorphism causing endothelial dysfunction in eclampsia. Methods. This cross-sectional study included 100 women with eclampsia and 100 healthy pregnant women. Their blood samples were analyzed for NO (indirectly), and inflammatory cytokines and eNOS (Glu298Asp) gene polymorphism were determined by DNA extraction, followed by restriction fragment length polymorphism. Results. Decreased NO metabolites and increased cytokines (tumor necrosis factor-α; interleukin-2, -6; and interferon-γ) levels were found in eclampsia (p < 0.001). Significant differences were found in genotype/allele distribution between the two groups. Occurrence of “T” allele frequency was found to be 0.27 among patients and 0.05 among controls (CI = 95%, OR = 0.7–0.9, p < 0.001). Significant negative correlation was seen between NO and cytokines levels (tumor necrosis factor-α and interferon-γ) in eclamptic women (p = 0.001). Conclusion. This study concluded that eclampsia is associated with decreased levels of NO and increased levels of circulating inflammatory cytokines, which might be contributed due to single-nucleotide polymorphism, pointing toward the role of endothelial and inflammatory components.

Association of endothelial dysfunction with endothelin, nitric oxide and eNOS Glu298Asp gene polymorphism in coronary artery disease.

The endothelial dysfunction has been implicated as a major event in the pathogenesis of atherosclerosis. Therefore, this study was planned to determine (a) role of endothelium-derived nitric oxide (NO) and endothelin as coronary artery disease (CAD) risk markers and (b) intergenotypic variation of endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism in CAD.The endothelin, NO and eNOS genotypes were determined in 60 patients with documented history of CAD. These were compared with 50 age- and sex- matched healthy controls. The genotype frequencies for eNOS gene polymorphism were determined by PCR and RFLP. The plasma endothelin in CAD patients was significantly higher (p < 0.001) whereas, the NO level in CAD group was significantly lower (p < 0.001) than the control group. The genotype frequencies for Glu298/Asp (Glu/Glu and Glu/Asp) genotypes were 75% and 25% in CAD subjects and 88% and 12% in control subjects, respectively. No Asp/Asp was found in any of the groups. The genotype frequencies differed significantly (p < 0.05) between the controls and cases. In conclusion, endothelin and NO may be used as markers of endothelial dysfunction in CAD. Asp allele might be a risk factor for CAD in the North Indian population.

Association of Endothelial Dysfunction with Endothelin, Nitric Oxide and eNOS Glu298Asp Gene Polymorphism in Coronary Artery Disease

The endothelial dysfunction has been implicated as a major event in the pathogenesis of atherosclerosis. Therefore, this study was planned to determine (a) role of endothelium-derived nitric oxide (NO) and endothelin as coronary artery disease (CAD) risk markers and (b) intergenotypic variation of endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism in CAD.The endothelin, NO and eNOS genotypes were determined in 60 patients with documented history of CAD. These were compared with 50 age- and sex- matched healthy controls. The genotype frequencies for eNOS gene polymorphism were determined by PCR and RFLP. The plasma endothelin in CAD patients was significantly higher (p&lt; 0.001) whereas, the NO level in CAD group was significantly lower (p&lt; 0.001) than the control group. The genotype frequencies for Glu298/Asp (Glu/Glu and Glu/Asp) genotypes were 75% and 25% in CAD subjects and 88% and 12% in control subjects, respectively. No Asp/Asp was found in any of the groups. The genotype frequencies differed significantly (p&lt; 0.05) between the controls and cases. In conclusion, endothelin and NO may be used as markers of endothelial dysfunction in CAD. Asp allele might be a risk factor for CAD in the North Indian population.

Lack of association between eNOS Glu298Asp gene polymorphism and carotid atherosclerosis in a Serbian population

; genepolymorphism.Endothelium-derived nitric oxide (NO), synthesizedbyendothelial NO synthase (eNOS), plays a crucial rolein regulating a wide variety of functions in the cardio-vascular system. A state of relative NO deficiency hasbeen linked to atherosclerosis, and has been equatedwith endothelial dysfunction (1).The

Relationship of endothelial nitric oxide synthase gene polymorphism with blood pressure, lipid profile and blood glucose level

To study the relationship of the polymorphism of endothelial nitric oxide synthase (eNOS) gene and blood pressure, lipid profiles and blood glucose level. By using PCR-RFLP, the eNOS Glu298Asp gene polymorphism was detected in 184 patients with essential hypertension and 196 matched healthy individuals with normal blood pressure. Taking into account eNOS Glu298Asp polymorphisms, the relationship of blood pressure with triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and blood glucose level was analyzed. The distribution of eNOS Glu298Asp polymorphism had no significant difference between different blood pressure groups and gender groups, but there was a significant difference between different age groups, diastolic blood pressure groups or BMI groups (P < 0.05). Asp/Asp genotype significantly increased the risk of hypertension in individuals with serum TC above 5.4 mmol/L (P = 0.03, OR = 2.65). eNOS Glu298Asp polymorphism and serum lipid could synergistically modulate the blood pressure. eNOS Asp/Asp genotype could significantly increase the risk of hypertension in individuals with serum TC over 5.4 mmol/L. eNOS Glu298Asp in combination with serum TC could be used to predict the risk of hypertension.

Association of eNOS Glu298Asp gene polymorphism with essential hypertension in Asian Indians

BackgroundSeveral reports suggested association between the T allele of the endothelial nitric oxide synthase gene polymorphism (eNOS) Glu298Asp (G→T at nucleotide 894, exon 7) with essential hypertension (EHT). Findings, however are not uniform. In this case–control study, we determined the prevalence and distribution of the above polymorphism and their relationship with the disease to elucidate the association of this polymorphism with the risk and pathophysiology of EHT in the Asian Indians and significance of T allele in this context. MethodsTwo hundred normal controls and 226 patients with EHT from Delhi and surrounding areas were recruited for the investigation. Venous blood samples were used for genotyping. Genotyping was done by PCR-RFLP. ResultsThe data suggested higher prevalence of GT+TT genotypes in patients as compared to the controls and association of T allele with EHT [p<0.001, odds ratio at 95% CI, 2.10 (1.34-3.28)]. ConclusionsAsian Indians of this region with T allele may be at higher risk of EHT.

Association of eNOS Glu298Asp gene polymorphism with circadian blood pressure rhythm

Hypertensive patients with altered circadian blood pressure (BP) profile experience greater repercussion of hypertension on target organs and a higher risk of cardiovascular events, compared with those with physiological variations in BP. It has been demonstrated in animal models, that circadian variations in BP depend on several regulatory systems, in particular the nitric oxide-cGMP pathway. eNOS298 Glu/Asp polymorphism is a functional variant and may alter the amount of NO generated or eNOS activity. The objective of the present study was to find out whether eNOS298 gene polymorphism affects circadian BP regulation in 110 healthy subjects and 155 never-treated hypertensive patients recruited at Hypertension Units in Grenoble, Toulouse and Lille (France).

Prevalence of eNOS Glu298Asp Polymorphism in Healthy Volunteers from a Region of Northern India

Objective: Endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphisms are under extensive study worldwide due to their suggested role in cardiovascular disorders. This polymorphism had gained more attention since several reports suggest its association with hypertension and coronary artery disease (CAD). Asian Indians are highly susceptible to ischemic heart dis eases. We determined the prevalence of eNOS Glu298 Asp polymorphism in 139 healthy volunteers from Delhi and the surrounding areas. The subjects were recruited from those who willingly participated in this study in response to a publicized call and a standard questionnaire. Male to female ratio was 2.7:1 due to the larger number of male participants in this investigation. This, however, does not represent normal male to female distribution in the area. Despite the male bias, this investigation was justified. The prevalence of CAD in males is about 3 times higher in this region and no data had so far been available on the distribution of this polymorphism from India. Method: The eNOS Glu298Asp polymorphism was studied by PCR-RFLP. Results: Distribution of genotype GG, GT and TT in the study subjects was found to be 71.22, 28.06 and 0.72%, respectively, and allele frequency was G,0.853;T,0.147. Conclusion: T allele had been described as susceptibility allele for CAD in several population studies. The frequency of the T allele was found to be two times higher in our subjects than that reported for Japanese and Korean populations. This study does not provide any direct evidence for eNOS gene disease associations but is the first report on the prevalence of eNOS Glu298Asp gene polymorphism in Indian subjects. Whether the observed pattern of eNOS Glu298Asp polymorphism contributes to the greater susceptibility of Asian Indians to CAD as compared to the other population groups, needs to be investigated.