Nitric Oxide Synthase Glu298Asp Gene Research Articles

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.

Association between Endothelial Nitric Oxide Synthase Gene Polymorphism (Glu298Asp) and Coronary No-Reflow Phenomenon in Acute Myocardial Infarction

No-reflow phenomenon is an important complication of primary percutaneous coronary intervention. Several variants in the endothelial nitric oxide synthase gene, which reduce endothelial nitric oxide synthase activity, are a risk factor for coronary heart disease. However, its role in no-reflow phenomenon has not yet been revealed. This study aimed to investigate whether there is a relationship between endothelial nitric oxide synthase Glu298Asp gene variant and the development of coronary no-reflow phenomenon in patients with ST elevation myocardial infarction. The study was conducted among 116 patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction. Group 1 included 52 ST elevation myocardial infarction patients undergoing no-reflow phenomenon as a study group. Group 2 comprised 64 ST elevation myocardial infarction patients without no-reflow phenomenon as a control group. Endothelial nitric oxide synthase was tested using polymerase chain reaction-restriction fragment length variant. The prevalence of TT genotype of endothelial nitric oxide synthase Glu298Asp gene variant was found to be significantly higher in patients developing coronary no-reflow when compared to those without no-reflow (p = 0.016; 11.54% vs. 1.56%) (OR = 10.85, 95% CI = 1.22–96.39). However, a similar association for the heterozygous GT genotype of endothelial nitric oxide synthase Glu298Asp gene variant was not observed between the two groups. The results of this preliminary study indicate that there is an association between Glu298Asp variant in endothelial nitric oxide synthase gene and the development of no-reflow phenomenon in ST elevation myocardial infarction. The presence of homozygous TT allele may contribute to tendency to the development of no-reflow phenomenon.

Endothelial nitric oxide synthase Glu298Asp gene polymorphism influences body composition and biochemical parameters but not the nitric oxide response to eccentric resistance exercise in elderly obese women

Both endothelial nitric oxide synthase (eNOS) gene polymorphism and nitric oxide (NO) are involved in important cardiovascular, muscular and inflammatory physiological mechanisms during ageing and response to exercise. The aim of this study was to investigate the NO kinetic response following an acute eccentric resistance exercise (ERE) session and the possible effect of the Glu298Asp eNOS gene polymorphism in elderly obese women. Eighty-seven women (age 69·4±6·1years, body weight 74·9±12·7kg, height 151·9±6·0cm and BMI 32·5±5·7kgm-2 ) completed seven sets of ten eccentric repetitions at 110% of the ten repetitions maximum (10RM). NO concentrations remained elevated up to 48h following the acute ERE session as compared with baseline, for GG and GT/TT groups (P<0·05), with no differences between genotypes. The GG genotype group had higher body weight, prevalence of obesity (BMI classification - 81% versus 56%), BMI and higher relative muscle strength, while they had significantly lower triglycerides, VLDL and urea concentrations as compared with TT/TG group. In conclusion, NO remains elevated for up to 48h after an acute ERE session, without genotype interaction. The TT/TG genotype had a negative impact on triglycerides, VLDL and urea concentrations. Thus, T carriers should increase their attention to cardiovascular risk factor and metabolic disorders.

Association of endothelial nitric oxide synthase Glu298Asp gene polymorphism in psoriasis cases with hypertension.

BACKGROUND AND OBJECTIVESPsoriasis is a common autoimmune-mediated chronic, inflammatory skin disease. Although, the molecular mechanism is not completely understood, psoriasis is caused by genetic and non-genetic parameters. The current study aimed (1) to define genotype and allele frequency of endothelial nitric oxide synthase (eNOS Glu298Asp) gene polymorphism in hypertensive and/or non-hypertensive psoriatic patients (2) to investigate the possible relationship between the eNOS Glu298Asp polymorphism and the risk of hypertension among psoriatic patients in the Turkish population.DESIGN AND SETTINGSThis cross-sectional, case-control study was performed between March 2010 and November 2012 at the University hospital in Çanakkale, TurkeyPATIENTS AND METHODSGene profiles of 75 psoriatic patients (21 hypertensive and 54 normotensive patients) and 55 healthy (normotensive and non-psoriatic) volunteers were compared. Peripheral blood-EDTA samples were used for total genomic DNA isolation and genotyping. Target eNOS gene was genotyped for patients and control groups by real-time PCR melting-curve analysis system (LightCycler 2.0, Roche, Germany, and results were compared statistically.RESULTSAn increased T allele frequency in eNOS Glu298Asp single-nucleotide polymorphism (SNP) was determined in psoriatic patients when compared with normotensive non-psoriatic healthy volunteers (OR 2.3, CI 1.14–3.99), (P=.017). The T allele frequency was also found to be increased in hypertensive psoriatic patients when compared with healthy volunteers (4.83-fold increased, 95% CI 1.62–14.43 ([P=.003]) and normotensive psoriatic patients (3.03-fold increased, 95% CI 1.03–8.94 [P=.041]), respectively.CONCLUSIONThe current preliminary results suggested that there was a correlation between eNOS Glu298Asp polymorphism and hypertension among psoriatic patients in the Turkish population. The T allele frequency of eNOS Glu298Asp SNP was different in hypertensive psoriatic patients, and the difference was statistically significant when compared with the normotensive psoriatic patients and healthy controls. These results need to be confirmed by large-scale studies.

Lack of role of endothelial nitric oxide synthase gene Glu298Asp polymorphism in rheumatoid arthritis among Asian Indians

Aim: The aim of this study was to investigate the association of Glu298Asp polymorphism in the endothelial nitric oxide synthase (eNOS) gene with rheumatoid arthritis (RA) in Asian Indians. Methods: We conducted a case control study in which 100 patients diagnosed with RA and 100 healthy controls were enrolled. DNA was extracted from peripheral blood and eNOS polymorphism was detected by PCR-RFLP. Plasma samples from the subjects were screened for nitric oxide (NO). Results: There was a trend of increase of GG genotypic and G allelic frequencies of the eNOS gene Glu298Asp in patients when compared with controls. GT genotype emerged as major genotype in both controls and patients. Genotypes disobeyed Hardy-Weinberg equilibrium. Reduced NO levels was detected in patients as compared to controls. Patients with GG genotype and GT genotypes were found to have significantly low level of plasma NO as compared to controls with GG and GT genotypes. Conclusions: eNOS gene Glu298Asp polymorphism is not associated with the susceptibility of rheumatoid arthritis in Asian Indians.

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 the endothelial nitric oxide synthase gene Glu298Asp polymorphism and coronary heart disease: A meta-analysis of 39 case-control studies

Numerous studies have indicated that the human endothelial nitric oxide synthase (eNOS) gene Glu298Asp polymorphism is associated with coronary heart disease (CHD) susceptibility, however, their conclusions are inconsistent. The present meta‑analysis aimed to evaluate the precise result by searching the PubMed database and using 39 case‑control studies comprising 7489 cases and 7051 controls.Each study tested the association between the eNOS Glu298Asp polymorphism and CHD. A meta‑analysis was then conducted using the Comprehensive Meta Analysis 2.2 software to calculate the pooled odds ratios (ORs) of five genetic models with 95% confidence intervals (CIs). Publication bias was also explored. The meta‑analysis showed a significant association between the eNOS Glu298Asp polymorphism and CHD susceptibility for all the genetic models [Asp vs. Glu, OR 1.26, 95% CI 1.14‑1.40, P<0.001; Asp/Asp vs. Glu/Glu, OR 1.58, 95% CI 1.23‑2.02, P<0.001; Glu/Asp vs. Glu/Glu, OR 1.12, 95% CI 1.03‑1.22, P=0.001; (Glu/Asp+Asp/Asp) vs. Glu/Glu, OR 1.17, 95% CI 1.07‑1.27, P<0.001; Asp/Asp vs. (Glu/Glu+Glu/Asp), OR 1.59, 95% CI 1.25‑2.03, P<0.001]. Subgroup and sensitivity analyses indicated that the result was robust. A weak publication bias was detected. The results indicated that the eNOS Glu298Asp polymorphism is a risk factor for developing CHD, particularly in the Asian population.

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.

Endothelial nitric oxide synthase Glu298Asp gene polymorphism in a multi-ethnical population with heart failure and controls

Brazilian population has a multi-ethnical profile and the prevalence of endothelial nitric oxide synthase enzyme (eNOS) polymorphism in heart failure (HF) has not been previously studied. Therefore the present study assessed the association of eNOS Glu298Asp polymorphism in patients with HF and controls. In a crossover study, was analysed the distribution of the Glu298Asp in 100 outpatients with HF, and 103 healthy controls. Self-reported race were analyzed. Left atria and left ventricle diameters and ejection fraction were evaluated in patients group. Glu298Asp was analysed by polymerase chain reaction and restriction fragment length polymorphism. The patient’s average age was 59 years, 66% males, 49% Afro-descendants. The allelic frequency in patient group was Glu298 = 72%/Asp298 = 28% and the genotype frequency (GF) was Glu298Glu:49%; Glu298Asp:47%; Asp298Asp:4%. In control group, 60% Glu298 and 40% Asp298; 35% Glu298Glu, 49.5% Glu298Asp and 15.5% Asp298Asp. The prevalence of allele Glu298 was significantly higher in patients ( p = 0.009) as genotype Glu298Glu ( p = 0.03). The Glu298 in Afro-Brazilians (79%) and white patients (67%) were similar, although there was significant difference ( p = 0.03) in GF Glu298Glu between Afro-Brazilians and whites. There was an increased prevalence of hypertension and increased atria in Glu298Glu patients comparing with combined genotype Glu298Asp and Asp298Asp. This study suggests a regional variation in the distribution of Glu298Asp. The comparison of this distribution in African-Brazilian suggests a synergistic effect of African-descendent, Glu298Glu genotype and HF. Also demonstrated an increased frequency of Glu298 and Glu298Glu, suggesting interaction of them with HF. In HF patients, the clinical, echocardiograph and genotype analysis suggests an association of Glu298 allele and hypertension.

Endothelial nitric oxide synthase gene Glu298Asp polymorphism in patients with coronary artery disease

Endothelial nitric oxide synthase gene Glu298Asp polymorphism in patients with coronary artery disease

Endothelial nitric oxide synthase gene Glu298Asp polymorphism in patients with coronary artery disease.

BACKGROUND AND OBJECTIVES:Endo-derived nitric oxide (NO) is synthesized from L-arginine by endothelial nitric oxide synthase (NOS3). Since reduced NO synthesis in endothelial cells has been implicated in the development of coronary atherosclerosis, we investigated the association of NOS3 gene polymorphisms and coronary artery disease (CAD) in an Iranian population.SUBJECTS AND METHODS:We studied the NOS3 gene Glu298Asp polymorphism in 241 CAD patients with positive coronary angiograms (i.e., >50% stenosis affecting at least one coronary vessel) in Shahid Rajaee Heart Hospital and 261 control subjects without a history of symptomatic CAD. The NOS3 gene polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Lipid profile and other risk factors were also determined.RESULTS:The genotype frequencies of Glu298Asp polymorphism for Glu/Glu, Glu/Asp, and Asp/Asp were 61.3%, 32.2%, and 6.5%, respectively, in control subjects, and 46.5%, 42.7%, and 10.8% in CAD patients, respectively. The genotype frequencies differed significantly between the two groups (P=.003). The frequencies of the Asp alleles were 32.2% and 22.6% for CAD patients and control subjects, respectively; the difference between the two groups was statistically significant (P=.001; odds ratio=1.6). Plasma lipids, except HDL-C, were also significantly increased in the CAD groups.CONCLUSION:These results suggest that CAD is associated with Glu298Asp polymorphism of the NOS3 gene in our population and that this polymorphism is an independent risk factor for CAD.

Endothelial nitric oxide synthase gene Glu298Asp polymorphism is associated with advanced stage endometriosis

Altered expression of endothelial nitric oxide synthase (eNOS) has been reported to be involved in the development of endometriosis. The genotypes of eNOS gene (NOS3) may be responsible for variation in its enzymatic activity as well as plasma concentration of nitric oxide. The Glu298Asp polymorphism of the NOS3 may modulate angiogenesis and influence individual susceptibility to endometriosis. This study was designed to evaluate the association between the Glu298Asp polymorphism of the NOS3 and advanced stage endometriosis. This study consisted of 299 women with advanced stage endometriosis and 459 control women without endometriosis in a Korean population. Genotyping results of the Glu298Asp polymorphism of the NOS3 were analyzed between the endometriosis and control group. The genotypic frequencies were significantly different between women with and without endometriosis. The frequency of the non-GG genotype (GT + TT) was higher in the endometriosis group than in the control group (P = 0.001). These findings suggest that the T allele, encoding aspartic acid, of the Glu298Asp polymorphism of the NOS3 may be associated with advanced stage endometriosis in the Korean population.

Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism is Associated with Hypertensive Response to Exercise in Well-Controlled Hypertensive Patients

PurposeHypertensive response to exercise (HRE) is known to be an adverse prognostic factor for future cardiovascular events and may be associated to endothelial dysfunction. Previous studies regarding endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism focused upon its relation to hypertension. In this study, we hypothesize that the polymorphism may be associated with inherent difference in endothelial response to exercise.Patients and MethodsTwo hundred sixty nine patients who underwent treadmill test were enrolled in this study; 77 patients (mean age 55.8 ± 9.4 years) had hypertensive response (peak systolic BP of ≥ 210mmHg in men and ≥ 190mmHg in women). Pulse wave velocity (PWV) was measured on 153 patients of them. The Glu298Asp exchange in exon 7 was determined by the methods of single base extension with amplifying primers and probes for TaqMan.ResultsThe percentages of the GG, GT and TT genotypes were 81.0, 18.6 and 0.4%, respectively. The presence of GT or TT genotype was independently associated with prevention of HRE when controlled for age, sex, baseline systolic BP and homeostatic model assessment (HOMA) index (OR = 0.35, p = 0.016). Subgroup analysis showed that preventive effect for HRE of T allele was significant in females (p < 0.001) and patients without insulin resistance (p = 0.009).ConclusionIn our study, eNOS Glu298Asp polymorphism was significantly associated with HRE. This result suggests that the presence of T allele of the Glu298Asp polymorphism may be a favorable factor to in preventing HRE, especially in female and patients without insulin resistance.

Autopsy and postmortem examination case study on genetic risk factors for cardiac death: Polymorphisms of endothelial nitric oxide synthase gene Glu298asp variant and T-786c mutation, human paraoxonas

The Glu298Asp variant in exon 7 and T-786C mutation in the 5'-flanking region of the endothelial nitric oxide synthase (eNOS) gene, paraoxonase I gene (PON1), and alpha2beta-adrenergic receptor gene (alpha2beta-AR) have been reported to be genetic risk factors for coronary heart disease (CHD). The aim of this study was to investige the effects of these four genetic polymorphisms on the probability of death due to CHD, using data obtained from medico-legal autopsies. Blood samples from three groups: healthy controls, dead cases with CHD and without CHD (the latter as a control for dead cases) were used. After DNA extraction, genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) test. The frequency of the T allele in Glu298Asp variant in the dead cases with CHD was significantly higher than that in the healthy control (p < 0.001, OR = 4.47) and that in the dead cases without CHD (p < 0.001, OR = 7.62). The gene frequency of PON1 was significandy different (p = 0.007) between dead cases with and without CHD, and was also significantly different (p = 0.025) between the healthy control and dead cases without CHD. The gene frequency of PON1 was not significantly different (p = 0.401) between the healthy controls and dead cases with CHD. Hence this gene was not associated with death due to CHD. The other polymorphisms (T-786C mutation, alpha2beta-AR) also showed no effect on death due to CHD. The polymorphism of Glu298Asp eNOS gene in dead cases may be useful for determining the cause of death in CHD cases in the Japanese population.

Endothelial nitric oxide synthase Glu298Asp gene polymorphism, blood pressure and hypertension in a general population sample

The Glu298Asp (E/D) polymorphism of the endothelial nitric oxide synthase (eNOS) gene has been related to hypertension. Since several studies have produced contradictory results, this issue is still subject to ongoing debate. We investigated the association of the eNOS E298D polymorphism with hypertension and with blood pressure (BP) in a large population-based sample of Caucasian ethnicity. Cross-sectional study in a random sample of the general population. The eNOS E298D polymorphism was determined by 5'-exonuclease assay among 4219 participants aged 20-79 years of the Study of Health in Pomerania (SHIP). The percentages of the EE298, ED298 and DD298 genotypes were 49.2, 42.0 and 8.8%, respectively. The D allele frequencies did not differ between the groups of normotensive and hypertensive subjects (29.7 versus 29.9%, P = 0.812). Similarly, no association could be established between E298D genotype and prevalent hypertension, neither for D allele carriership (multivariate odds ratio 0.97, 95% confidence interval 0.83-1.12) nor for DD homozygosity (multivariate odds ratio 1.10, 95% confidence interval 0.84-1.43). Likewise, genotype groups did not differ as to the distribution of systolic (ANCOVA P = 0.917) or diastolic BP values (ANCOVA P = 0.657). Nearly identical results were obtained if the analyses were repeated sex-specifically or if subjects on antihypertensive medication were excluded. In a population-based cohort of Caucasians covering a broad age range, the eNOS E298D polymorphism is neither associated with prevalent hypertension nor with systolic or diastolic BP. These results do not support the hypothesis that the E298D polymorphism contributes to the genetic susceptibility to hypertension.

Ambulatory blood pressure, left ventricular mass and vascular phenotypes in relation to the endothelial nitric oxide synthase gene Glu298Asp and intron 4 polymorphisms in a population-based family study

Reduced nitric oxide production is associated with pathological changes in the cardiovascular system. In a study of randomly chosen families, we analysed the relationship between two polymorphisms (Glu298Asp and intron 4) of the endothelial nitric oxide synthase (eNOS) and ambulatory blood pressure (ABP), left ventricular mass index (LVMI) and vascular phenotypes. The study population consisted of 127 parents and 167 offspring. All subjects underwent 24 h ABP monitoring using a SpaceLabs 90207 device. 2D and M-mode echocardiograms were obtained. Pulse wave velocity between the common carotid and femoral artery was measured with the Complior device, and the carotid intima-media thickness (IMT) was assessed by ultrasound. For statistical analysis, covariables and correlations between relatives were taken into account. The frequency of genotypes was as follows: for Glu298Asp: 55.1%-Glu/Glu, 40.1%-Glu/Asp and 4.8%-Asp/Asp; for intron 4: 65.0%-4 b/b, 33.3%-4 b/a and 1.7%-4 a/a, being in Hardy-Weinberg equilibrium (P > or = 0.29). There was no relationship between the eNOS gene polymorphisms and ABP or LVMI either in parents or their offspring. Among parents, carriers of the 298Asp allele had higher IMT values as compared with Glu/Glu homozygotes (0.94 vs 0.70 mm; P = 0.007). Among offspring, there was a similar tendency (0.60 vs 0.53 mm; P = 0.10), which was confirmed by transmission disequilibrium tests for quantitative variables (P > or = 0.07). Our findings indicate that the Glu298Asp polymorphism of eNOS identifies patients with larger carotid IMT, also in younger subjects.

Endothelial nitric oxide synthase gene Glu298Asp polymorphism and blood pressure, left ventricular mass and carotid artery atherosclerosis in a population-based cohort.

Decreased production of endothelial nitric oxide (NO) is associated with different cardiovascular pathology. We studied the association between the Glu298Asp polymorphism of the NO producing gene, endothelial nitric oxide synthase (eNOS), and hypertension, left ventricular mass (LVM) and carotid artery intima-media thickness (IMT) in a population-based cohort of hypertensive and control subjects. Cross-sectional case-control study. District around Oulu University Hospital, Northern Finland. The study population consisted of 600 middle-aged hypertensive subjects (300 men and 300 women) and 600 controls (300 men and 300 women) living in the City of Oulu. The hypertensive subjects were randomly selected by age stratification from the Social Insurance Institute register for reimbursement of antihypertensive medication. For each hypertensive subject, an age- and sex-matched control was randomly selected from the national health register. The overall participation rate was 87.8%. In the present study a total of 1024 subjects were screened. Echocardiographic examinations were performed by a trained cardiologist and carotid ultrasonographic examinations by a trained radiologist. The genotype distributions and allele frequencies between the hypertensive and control subjects and the relationship between the Glu298Asp variant and blood pressure, LVM and carotid artery IMT were determined. No differences in genotype distribution or allele frequencies were found between the hypertensive and control groups (the frequency of the Asp allele 0.299 vs. 0.288, respectively). Also, we could not find any association between the eNOS genotype and the measured cardiovascular complications. The Glu298Asp variant of the eNOS gene does not seem to be a major risk factor for cardiovascular alterations in the general population.