eNOS G894T Research Articles

Associations of the eNOS G894T gene polymorphism with target organ damage in children with newly diagnosed primary hypertension.

BackgroundThe endothelial nitric oxide synthase (eNOS) G894T gene polymorphism is associated with the risk of primary hypertension (PH) and vascular complications in adults with PH.MethodsWe explored the associations of the G894T polymorphism with 24-h ambulatory blood pressure, left ventricular mass (LVM), carotid intima media thickness (cIMT), urinary albumin excretion, oxidative stress and inflammatory parameters in 126 children with newly diagnosed PH and in 83 healthy children.ResultsAmong the 126 children with PH 92 (73 %) had ambulatory hypertension and 34 (27 %) had severe ambulatory hypertension. Left ventricular hypertrophy (LVH) was detected in 39 (31 %) patients, cIMT of >2 standard deviation scores in 21 (16.6 %) patients, albuminuria of >30 mg/24 h in 18 (14.3 %) patients and metabolic syndrome (MS) in 22 (17.5 %) patients. The frequency of the T allele was 52.4 % in the PH group and 54.2 % in the control group (not significant), and in both groups the frequency of the T allele was consistent with the Hardy–Weinberg equilibrium. Compared with G allele carriers, hypertensive T allele carriers had increased cIMT (p < 0.05) and more severe albuminuria (not significant, p = 0.1); there was no difference between the groups in hypertension severity and LVM. T and G allele distribution did not differ between patients with and without metabolic syndrome. No significant correlations between the assessed parameters and the eNOS G894T gene polymorphism were found in the controls, although T allele carriers tended to have an increased cIMT (p = 0.09).ConclusionThe eNOS T allele is not more prevalent among hypertensive children than among healthy ones, but it is associated with early vascular damage in children with PH, independent of metabolic abnormalities. No associations between the eNOS G894T polymorphism and metabolic abnormalities were found.

Changes of soluble CD40 ligand in the progression of acute myocardial infarction associate to endothelial nitric oxide synthase polymorphisms and vascular endothelial growth factor but not to platelet CD62P expression

Reported in vitro data implicated soluble CD40 ligand (sCD40L) in endothelial dysfunction and angiogenesis. However, whether sCD40L could exert that influence in endothelial dysfunction and angiogenesis after injury in acute myocardial infarction (AMI) patients remains unclear. In the present study, we evaluated the association of sCD40L with markers of platelet activation, endothelial, and vascular function during a recovery period early after AMI. To achieve this goal, the time changes of soluble, platelet-bound, and microparticle-bound CD40L levels over 1 month were assessed in AMI patients and correlated with endothelial nitric oxide synthase (eNOS) polymorphisms, vascular endothelial growth factor (VEGF) concentrations, and platelet expression of P-selectin (CD62P). The association of soluble form, platelet-bound, and microparticle-bound CD40L with CD62P expression on platelets, a marker of platelet activation, was also assessed to evaluate the role of CD40L in the thrombosis, whereas the association with eNOS and VEGF was to evaluate the role of CD40L in vascular dysfunction. This work shows for the first time that time changes of sCD40L over 1 month after myocardial infarct onset were associated with G894T eNOS polymorphism and with the VEGF concentrations, but not to the platelet CD62P expression. These results indicate that, in terms of AMI pathophysiology, the sCD40L cannot be consider just as being involved in thrombosis and inflammation but also as having a relevant role in vascular and endothelial dysfunction.

Endothelial nitric oxide synthase genotypes modulate peripheral vasodilatory properties after myocardial infarction

BackgroundStudies in population genetics suggest an important relationship between the eNOS G894T polymorphism and occurrence of acute myocardial infarction (AMI), with little known on its influence on the post-AMI period. AimTo investigate the association of allelic variants produced by the G894T transversion in eNOS (rs1799983) with post-AMI variables. MethodsCross-sectional analyses of anthropometric, clinical and laboratory assessments obtained within the first 24h and after 5 and 30days of the AMI event across T carriers and G homozygotes of eNOS in 371 consecutive cases of AMI with ST-segment elevation admitted to a Brazilian emergency service in cardiology. Genotypes were determined by polymerase chain reaction followed by enzymatic restriction. ResultsDespite no difference between genotypic groups on aspects as Killip–Kimbal classification scores, extension of infarcted mass, lipid profile or pattern of medication use, an increase in serum nitric oxide from admission to day 5 was higher for T carriers (p<0.001). Thirty days post-AMI, peripheral blood flow reserve was larger among T carriers either by flow- (p=0.037) and nitrate-mediated (p=0.040) dilation testing. ConclusionOur results suggest an association of the eNOS 894T allele with an apparent improvement in late arterial function in post-AMI patients.

Endothelial nitric oxide synthase polymorphism and prognosis in systolic heart failure patients

BackgroundThe endothelial nitric oxide synthase (eNOS) gene single nucleotide polymorphism G894T is associated with thrombotic vascular diseases. However, its functional significance is controversial and data are scarce concerning its influence in heart failure (HF). MethodsWe studied 215 patients with chronic systolic HF. DNA was analyzed for eNOS gene G894T polymorphism using PCR and DNA sequencing. Evaluation of clinical characteristics and analysis of factors associated with 2-year mortality were performed for the homozygous G-allele G894T variant (GG), relative to the TT and GT variants. ResultsThe genotype distributions of eNOS G894T alleles were: GG 135 patients (63%) and TT/GT 80 (37%). Two-year mortality was significantly higher in the GG variant (48%) than the combined TT/GT group (32%). The usage of nitrates was associated with increased 2-year mortality (HR 2.0, 95% CI 1.28–3.17; p = 0.003), which was most significant in the GG group treated with nitrates (73.5%) in comparison to the TT/GT group not treated with nitrates (34%); HR 2.75, 95% CI 1.57–4.79, P < 0.001. ConclusionsHomozygosity for the G allele of the eNOS G894T polymorphism was associated with worse survival in systolic HF patients, especially in those treated with nitrates. ENOS polymorphism may result in different mechanistic interactions in HF than in thrombotic vascular diseases, suggesting that overexpression of NO may be associated with deleterious effects in systolic HF.

Endothelial Nitric Oxide Synthase Gene Polymorphism Relationship With Semen Parameters and Oxidative Stress in Infertile Oligoasthenoteratozoospermic Men

To assess endothelial nitric oxide synthase (eNOS) gene polymorphism relationship with semen parameters and oxidative stress in infertile oligoasthenoteratozoospermic (OAT) men. Three hundred subjects were divided into healthy fertile men (n = 80) and infertile OAT men (n = 220). They were subjected to history taking, clinical examination, and semen analysis in addition to malondialdehyde and glutathione peroxidase estimation in seminal plasma. Polymorphisms of eNOS G894T and T786C genotypes in peripheral blood were identified by the polymerase chain reaction-restriction fragment length polymorphism analysis. Comparing infertile OAT men with fertile controls, eNOS genotype G894T demonstrated prevalence of 36.8% vs 50% for wild type (GG), 35.0% vs 47.5% for heterozygous type (GT), and 28.2% vs 2.5% for mutant homozygous type (TT). Compared with GG homozygotes, carriers with A allele exhibited >1.716-fold increased risk of OAT occurrence. Comparing infertile OAT men with fertile controls, eNOS genotype T786C demonstrated prevalence of 37.3% vs 51.3% for wild type (TT), 32.7% vs 45% for heterozygous type (TC), and 30% vs 3.7% for mutant type (CC) with significant differences. Compared with TT homozygotes, carriers with C allele exhibited >1.769-fold increased risk of OAT occurrence. G894T and T786C genotypes demonstrated significant negative correlation with sperm count, total sperm motility, sperm normal forms, and seminal glutathione peroxidase, and significant positive correlation with seminal malondialdehyde. G894T genotype demonstrated significant positive correlation with T786C genotype. There is a significant relationship between eNOS genotypes T786C, G894T polymorphisms with decreased sperm parameters and increased seminal oxidative stress.

An Updated Meta-Analysis of the Effects of the Endothelial Nitric Oxide synthase Gene G894T Polymorphism and Erectile Dysfunction Risk.

Erectile dysfunction (ED) is a common disorder leading to a serious and negative impact on the patient's quality of life. The gene encoding endothelial nitric oxide synthase (eNOS) is an interesting candidate gene for understanding the physiopathology of ED. However, an association between eNOS G894T polymorphism and ED risk is uncertain and should be updated. Therefore, a meta-analysis of the current literature was necessary to clarify this relationship. We searched Pubmed and China National Knowledge Infrastructure (CNKI) (last search updated on Dec 12, 2013) using 'nitric oxide synthase,' 'polymorphism or variant,' 'genotype,' and 'ED' as keywords. We also searched reference lists of studies corresponding to the inclusion criteria for the meta-analysis. These studies involved the total number of 1,445 ED men and 1,459 healthy control men subjects. Odds ratio (OR) and 95% confidence intervals (CIs) were used to evaluate this relationship. Statistical analysis was performed with STATA10.0. In the overall analysis, significantly decreased associations between ED risk and eNOS G894T polymorphism were found. Moreover, in the subgroup analysis based on ethnicity, similar significant associations were detected in both Caucasians (such as GG+GT vs. TT: OR 0.92, 95%CI 0.86-0.97) and Asians (such as GG+GT vs. TT: OR 0.24, 95% CI 0.07-0.85). The Egger's test did not reveal the presence of a publication bias. Our investigations demonstrate that eNOS G894T polymorphism might protect men against ED risk. Further studies based on larger sample size and gene-environment interactions should be conducted.

Relationship between eNOS 894G&amp;gt;T Polymorphism and the Antihypertensive Efficiency of Two Dihydropyridine Calcium Channel Blocker Drugs, Azelnidipine and Nitrendipine, in Chinese EH Patients

Background: Dihydropyridine calcium-channel blockers (dCCBs) were widely used in anithypertensive treatment. The aim of this study was to examine the effect of polymorphisms of CACNA1C, eNOS and RGS2 on the antihypertensive efficiency of dihydropyridine calcium channel blocks (dCCBs) in Chinese patients with essential hypertension (EH). Methods: A total of 107 untreated Chinese mild to moderate EH patients were enrolled in this study, and had been prescribed azelnidipine or nitrendipine as monotherapy. All patients who had gave informed consent for genetic research were divided into two groups: treated with azelnidipine or nitrendipine for at leaset 6 weeks. Five polymorphisms of three blood pressure (BP) and hypertension susceptible genes were studied in our research, and these polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Every patients’ BP and heart rate were measured at 0 week, 2 weeks, 4 weeks and 6 weeks. The biochemical parameters of blood were detected before and 6 weeks after the administration. Adverse effects were evaluated at the last visitation. Results: Both the systolic and diastolic BP levels were significanlty decreased after six weeks of dCCBs treatment, from 149.3 ± 9.2 mmHg to 132.2 ± 11.7 mmHg and form 97.9 ± 3.0 mmHg to 85.5 ± 7.5 mmHg, as well as the levels of TP, TBIL, CHO and LDL, the P-values were P=0.017, P=0.045, P=0.039, P=0.041 respectivley. As 11 of 75 patients appeared adverse reactions, the rate of adverse effects showed no difference in various genotypes. There were significant interactions between eNOS G894T polymorphism and △DBP, △MBP on azelnidipine therapy patients, but not in nitrendipine, the GG genotype carriers were more sensitive in blood decrease than GT/TT genotype carriers (P<0.05). Conclusion: CCBs had potential hepatoprotective and antiatheroscloresis effects for Chinese EH paitents. And the eNOS G894T polymorphism is associated with the hypotensive effect of azelnidipine.

The G894t, T-786c and 4b/a polymorphisms in Enos gene and cancer risk: a meta-analysis.

Published results on association between eNOS polymorphisms and cancer risk are conflicting. We aimed to investigate the association and give an overall understanding of possible risk role of eNOS. We searched PubMed and EMbase databases. The pooled ORs and 95% CIs for the association between eNOS polymorphisms and cancer risk was estimated using fixed- or random- effect model. Subgroup and sensitivity analyses were employed for further analysis. The Overall results showed no significant association of G894T polymorphism with cancer susceptibility (T vs. G: OR 1.02, 95% CI 0.97 to 1.07; TT+GT vs. GG: OR 1.02, 95% CI 0.96 to 1.09; TT vs. GT+GG: OR 1.05, 95% CI 0.93 to 1.17). For the T-786C polymorphism, pooled OR under recessive model suggested that CC genotype was significantly associated with increased cancer risk (CC vs. TC+TT: OR 1.31, 95% CI 1.09 to 1.57). For the 4b/a polymorphism, pooled OR for recessive model suggested positive result of 4a/4a genotype (aa vs. ba+bb: OR 1.64, 95% CI 1.11 to 2.43). In subgroup analysis by ethnicity, significant association was found in Caucasians in recessive model but not in Asians for T-786C and 4b/a, respectively. In subgroup analysis by cancer types, significant result was obtained for breast cancer in recessive model for the T-786C polymorphism. The eNOS G894T polymorphism may not be a major risk factor for most types of cancers. The CC of T-786C polymorphism and 4a/4a of 4b/a polymorphism are associated with cancer risk, especially in Caucasians. There is significant association between T786C polymorphism and breast cancer risk. More data are needed to verify these results.

INOS and eNOS Genotypes and Expression in Hepatitis E-Related Acute Liver Failure

Introduction: The study was aimed to determine the role of iNOS and eNOS genotypes in their expression in hepatitis E virus (HEV)-related acute liver failure (ALF). Methods: The study group included 294 acute viral hepatitis (AVH), 82 ALF and 331 healthy controls. Expression study of iNOS and eNOS was done using commercially available ELISA kits. Polymorphism of iNOS C150T and eNOS G894T was studied using the PCR-RFLP method. Determination of the iNOS and eNOS gene mutations was done using the TSP509I restriction enzyme for iNOS and Ban II restriction enzyme for eNOS. Pearson correlation analysis was done to observe the correlations between iNOS and eNOS with the parameters for the severity of disease (viral load, prothrombin time, total bilirubin, SGOT, SGPT, and ALP). Results: On comparing the iNOS levels corresponding to its genotype in the study group, we observed that the subjects carrying the CT+TT mutant genotype had significantly higher levels of iNOS compared to the wild type CC genotype (24.9± 6.9 vs.16.74±5.1; p<0.001, 62.16±1.6 vs. 54.26 ±6.1, p<0.001, and 10.57±5.15 vs.7.36±2.5, p<0.001). Similarly, on comparing the eNOS levels corresponding to its genotype in the study groups, we observed that the subjects carrying the GT+TT mutant genotype had significantly higher levels of eNOS compared to the wild type GG genotype (27.3± 7.2 vs.21.45±5.1, p<0.001, 64.1±1.8 vs. 58.5 ±2.8, p<0.001 and 17.9±4.8 vs.14.6±4.3, p<0.001). Significant positive correlation was observed between the iNOS and eNOS levels in the HEV-infected patient (AVH and ALF) and the severity of disease parameters i.e viral load, prothrombin time, total bilirubin, direct bilirubin, SGOT, and SGPT levels. Conclusion: iNOS and eNOS mutant genotype significantly increases the levels of iNOS and eNOS, as compared to wild type. The iNOS C150T polymorphism and the eNOS G894T polymorphism and high levels of iNOS and eNOS are associated with an increased risk of HEV-related acute hepatitis and liver failure.

Endothelial nitric oxide synthase 894 G > T polymorphism and thrombotic disease: A Meta-Analysis of 17 studies involving 8808 subjects

IntroductionEndothelial nitric oxide synthase (eNOS) 894G>T polymorphism may influence the risk of thrombotic disease, but data from published studies with low statistical power are inconclusive. To investigate the association between the gene polymorphism and thrombotic disease, a meta-analysis was performed. Materials and MethodsCase–control studies evaluating the association between the eNOS G894T polymorphism, Glu298Asp and thrombotic disease were searched in PubMed, OVID, Web of Science, Google Scholar and China Biology Medicine disc (CBM). Data were available for 4742 cases and 4066 controls from 17 studies. ResultsIn all, although there was a significant association between G894T and thrombotic disease (G/T+T/T vs. G/G: OR=1.364, 95%CI=1.126-1.652, P=0.001; T/T vs. G/T+G/G: OR=1.861, 95%CI=1.207-2.870, P=0.005; TT vs. GG: OR=1.938, 95%CI=1.244-3.021, P=0.003; G/T vs. G/G: OR=1.225, 95%CI=1.022-1.469, P=0.028), there was significant heterogeneity among studies (P*<0.001). In subgroup analysis, there was significant association with no heterogeneity in venous thrombosis (G/T+T/T vs. G/G: OR=1.409, 95%CI=1.135-1.750, P=0.002, P*=0.508; T/T vs. G/G: OR=1.640, 95%CI=1.011-2.660, P=0.045, P*=0.333; G/T vs. G/G: OR=1.357, 95%CI=1.082-1.701, P=0.008, P*=0.595) and in Asian population (G/T+T/T vs. G/G: OR=1.722, 95%CI=1.443-2.055, P<0.001, P*=0.541; T/T vs. G/T+G/G: OR=2.357, 95%CI=1.389-4.000, P=0.001, P*=0.908; T/T vs. G/G: OR=2.813, 95%CI=1.645-4.810, P<0.001, P*=0.969; G/T vs. G/G: OR=1.645, 95%CI=1.370-1.975, P<0.001, P*=0.489). ConclusionsFindings of this meta-analysis demonstrated that eNOS G894T polymorphism may be a risk factor for venous thrombosis, and in Asia the polymorphism may increase the risk of developing thrombotic disease.

The role of endothelial nitric oxide synthase gene G894T and intron 4 VNTR polymorphisms in hemodialysis patients with vascular access thrombosis.

Endothelial nitric oxide synthase (eNOS) gene is a candidate gene in cardiovascular and renal diseases. Several polymorphic variations have been identified in eNOS gene. We investigated a potential role of arteriovenous fistula (AVF) thrombosis and intron 4 and G894T polymorphisms in chronic renal failure. We performed a case-control observational study involving 79 with/without AVF thrombosis in chronic renal failure patients. All subjects were genotyped by the polymerase chain reaction (PCR) and PCR-Restriction Fragment Length Polymorphism. Genotype distribution and allele frequencies were compared between groups using the chi-square test. Genotype frequencies in patients with thrombosis were not significantly different from those of patients without thrombosis for eNOS G894T polymorphism (p=0.1). eNOS gene intron 4 a allele distributions seems to be associated with thrombosis in the groups. This study revealed that there was an association between eNOS intron 4 polymorphism and thrombosis in chronic renal failure patients. This data will be helpful in planning further eNOS association studies in vascular access thrombosis.

G894T endothelial nitric oxide synthase polymorphism and ischemic stroke in Morocco

Nitric oxide plays a major role in the regulation of cerebral blood flow and loss of its function leads to alteration of the vascular relaxation given its central role in the physiology of the vascular system. G894T eNOS polymorphism could have adverse effects on the expression and activity of endothelial nitric oxide synthase, which can result in functional impairment of the endothelium and contribute to the development of ischemic stroke in the different models of transmission.In this study, genotyping with PCR-RFLP and HRM (high resolution melting) methods were conducted on 165 ischemic stroke patients as well as 182 controls. The goal here was to compare genotyping with PCR-RLFP primer sequences of eNOS gene (size<300bp) to HRM.Our data suggests a statistically significant association between G894T eNOS polymorphism and ischemic stroke in recessive, dominant and additive models with P<0.05 and odds ratio of 2.68 (1.08–6.70), 1.78 (1.16–2.73), and 1.71 (1.21–2.43) respectively.In sum, although the sample size is relatively small, it suggests that G894T eNOS polymorphism could be a potentially important genetic marker of ischemic stroke in the Moroccan population. Future studies should be conducted in this direction taking into consideration the functional activity of eNOS.

Endothelial nitric oxide (eNOS) gene G894T and VNTR polymorphisms are closely associated with the risk of ischemic stroke development for Asians: meta-analysis of epidemiological studies

Although the relationships between endothelial nitric oxide synthase (eNOS) gene polymorphisms (including G894T, VNTR and T786C) and risk of ischemic stroke (IS) have been extensively studied, controversial results have been reported. The aim of this study was to assess the relationships between them by using a meta-analysis. Literatures were retrieved through the following databases: Medline, Embase and Wangfang (updated to January 1st, 2013). Fixed- or random-effects model was used to calculate pooled odds ratio and 95 % confidence interval (OR and 95 % CI). A total of 31 case-control studies including 8,547 patients and 9,117 controls were included in this meta-analysis eventually. For eNOS G894T polymorphism, the results indicated that TT genotype was significantly associated with increased risk of IS incidence compared to G allele (OR and 95 % CI 1.25 (1.09-1.42) for TT vs. GT+GG, P < 0.001). When subgroup analysis was conducted according to ethnicities, T allele was significantly associated with risk of IS for Asians rather than for Caucasians. For eNOS VNTR polymorphism, 4aa genotype was significantly associated with risk of IS incidence compared to 4bb genotype (OR (95 % CI) 2.22 (1.66-2.97) for aa vs. bb, P < 0.001). Similarly, when subgroup analyses were conducted, 4aa was closely associated with increased risk of IS for Asians rather than for Caucasians. For eNOS T786C polymorphism, it was not associated with risk of IS incidence. In conclusion, this study indicated that eNOS 894T and VNTR 4a allele was significantly associated with risk of IS incidence for Asians. However, eNOS T786C polymorphism was not a likely risk factor for IS incidence.

Endothelial Nitric Oxide Synthase Gene G894T Polymorphism and Myocardial Infarction: A Meta-Analysis of 34 Studies Involving 21068 Subjects

BackgroundResearches have revealed that the endothelial nitric oxide synthase (eNOS) gene G894T polymorphism is associated with the risk of Myocardial infarction (MI), but the results remain conflicting.Objective and MethodsA meta-analysis was conducted to investigate the association between eNOS G894T polymorphism and MI. Published studies from PubMed, Embase, CNKI and CBM databases were retrieved. The pooled odds ratios (ORs) for the association between eNOS G894T polymorphism and MI and their corresponding 95% confidence intervals (CIs) were estimated using the random- or fixed- effect model.ResultsA total of 34 studies including 8229 cases and 12839 controls were identified for the meta-analysis. The eNOS G894T polymorphism was significantly associated with MI under a homozygous genetic model (OR = 1.41, 95% CI = 1.08–1.84; P = 0.012), a recessive genetic model (OR = 1.35, 95% CI = 1.06–1.70; P = 0.014), a dominant genetic model (OR = 1.18, 95% CI = 1.04–1.34; P = 0.009). In the subgroup analysis by ethnicity (non-Asian and Asian), no significant association was observed between eNOS G894T polymorphism and MI risk among non-Asians (P>0.05), but a positive significant association was found among Asians (P<0.05).ConclusionsThe eNOS G894T polymorphism is associated with increased MI risk in Asians. The results indicate that ethnicity plays important roles in the association between eNOS G894T polymorphism and MI.

Genetic variants of the endothelial NO synthase gene (eNOS) may confer increased risk of sporadic congenital heart disease.

The endothelial NO synthase (eNOS) enzyme is expressed during the early stages of cardiogenesis and plays an important role in normal heart development. Genetic variations of eNOS G894T have been shown to influence individual susceptibility to some phenotypes of congenital heart disease (CHD) in different populations. We conducted a case-control study comprised of 945 CHD patients and 972 non-CHD individuals in a Chinese population. Two functional single nucleotide polymorphisms (SNPs) (T-786C: rs2070744 and G894T: rs1799983) and one tagging SNP (rs7830) were evaluated in our study, and we assessed their association with the risk of CHD. Compared with the rs7830 CC/AC genotypes, the eNOS rs7830 AA genotype showed a significantly increased risk of CHD (adjusted odds radio (OR) = 1.45, 95% confidence interval (CI = 1.13-1.85). A stratified analysis was performed and showed that the association between the rs7830 AA genotype and CHD risk was stronger in patients with perimembranous ventricular septal defects (adjusted OR = 1.62, 95%CI = 1.20-2.20). Our results suggest that the eNOS rs7830 polymorphism may contribute to the susceptibility of sporadic CHD in a Chinese population.

Role of nitric oxide synthase genes in hepatitis E virus infection

Hepatitis E virus (HEV) is the most common cause of endemic and epidemic acute hepatitis. A correlation between iNOS, eNOS polymorphisms, levels and severity of disease has been reported, and here, we examined the role of iNOS and eNOS gene polymorphisms and their levels in HEV-related acute viral hepatitis and acute liver failure. Hepatitis E virus-related cases of acute hepatitis (294 patients) and liver failure (82 patients) and age- and sex-matched healthy controls (331 subjects) were included in the study. PCR-RFLP was performed to identify the polymorphisms in the iNOS and eNOS genes. iNOS and eNOS levels were studied using ELISA assays and HEV viral load, genotype and combined effects of iNOS genotype, levels and parameters for disease severity were examined. The frequency of iNOS (CT + TT) and eNOS (GT + TT) genotypes was higher in subjects with liver failure compared with controls. iNOS and eNOS levels in patients with acute liver failure (55.51 ± 6.33 IU/mL, 60.2 ± 3.69) cases were significantly increased as compared to patients with acute viral hepatitis (17.8 ± 6.08 IU/mL, 23.7 ± 6.57) and controls (P < 0.05). A significant positive correlation was observed between the iNOS and eNOS levels in our study population when compared with the severity of disease parameters. Hence, the iNOS C150T polymorphism and the eNOS G894T polymorphism and high levels of iNOS and eNOS are associated with an increased risk of HEV-related acute hepatitis and liver failure. This study supports the possible role of nitric oxide synthase genes (iNOS and eNOS) in determining the severity of HEV infection.

Impact of endothelial nitric oxide synthase gene polymorphism on severity of enterovirus 71-infection in Chinese children

ObjectivesGenetic polymorphism G894T on the endothelial nitric oxide synthase (eNOS) gene has been reported as a susceptibility factor in a number of diseases, but evidence of its effect on enterovirus 71 (EV71) infection is lacking. This study investigated the possible association between this polymorphism (rs1799983) and disease severity in Chinese children with EV71 infection. Design and methods185 children with EV71 infection (83 with severe and 102 with mild disease) and 234 control healthy children underwent testing with polymerase chain reaction–restriction fragment length polymorphism (PCR–RLFP) to detect G894T polymorphism. In addition, plasma levels of nitric oxide (NO), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and serum eNOS activity were measured according to genotype. ResultsThe presence of GT+TT genotypes and T allele were associated with severe cases compared to genotype GG (OR 2.5, 95% CI 1.2–5.3, P=0.017) and G (OR 2.4, 95% CI 1.2–4.8, P=0.011). Furthermore, in EV71 encephalitis, GT+TT genotype and T allele were also more frequent than GG and G (P<0.05). The NO level and eNOS activity in T carriers (GT+TT) (84.3±2.5μmol/L and 14.4±1.8U/mL) were significantly less compared to in G carriers (GG) (92.0±1.5μmol/L and 19.1±1.7U/mL, P<0.001). But T carriers had higher plasma levels of IL-1β, IL-6, and TNF-α than people without a T allele (P<0.001), and a significant negative correlation was observed between NO and cytokine levels. ConclusionThe results indicate that carrying the T allele of the eNOS G894T gene polymorphism was associated with EV71 infection, and could be a susceptibility factor in the development of EV71 infection in Chinese children.

Presence of eNOS TT genotype is associated with a poor prognosis in patients with a previous myocardial infarction

Purpose: The G894T polymorphism of eNOS resulting from G to T conversion at nucleotide 894 of exon 7 of the gene is an important polymorphism of eNOS. It has been suggested that in the presence of eNOS TT genotype, there is a significant decrease in the amount of eNOS or its enzymatic activity. Therefore the purpose of this study was to assess the long-term predictive value for cardiovascular disease (CVD) of G894T eNOS polymorphism in patients with previous myocardial infarction. Methods: DNA was extracted from the whole EDTA blood. The variant of eNOS gene being analyzed was the G894T, in which a substitution of G to T at nucleotide position 894 results in a replacement of glutamic acid for aspartic acid at codon 298 (Glu298Asp) in the encoded protein. This 894G/T polymorphism in exon 7 of the eNOS gene was genotyped by standard polymerase chain reaction (PCR) amplification and detected by restriction fragment length polymorphism in 109 patients with a previous myocardial infarction. Results: The GG genotype was found in 51 patients and the GT genotype was found in 49 patients, whereas nine of the 108 patients had the TT type. Over 8.4 years of follow-up, 23 patients reached the primary endpoint of a hard CVD endpoint (cardiovascular death from any cause, nonfatal myocardial infarction or stroke). In the TT group 55.6% of the patients had a hard event, whereas 18.0% had a hard event among the rest of the patients (GG/GT) (p<0.05). None of the other measured standard cardiovascular risk factors differed significantly between the TT group and the GT/GG group. Conclusions: The presence of eNOS TT genotype was associated with a significant worse prognosis after 8.4 years follow-up in patients with a previous myocardial infarction.

Analysis of endothelial nitric oxide synthase (eNOS) G894T polymorphism and semen parameters in a Chinese Han population

Previous studies have shown that endothelial nitric oxide synthase (eNOS) gene may be involved in abnormal semen parameters. However, the relationship between eNOS G894T polymorphism and semen parameters remains controversial. The purpose of this study was to investigate the association of eNOS G894T polymorphism and semen parameters. The genotype frequency of eNOS G894T was determined in 270 idiopathic asthenozoospermia patients and 248 ethnically matched healthy volunteers using iPLEX genotyping assays on a MassARRAY(®) (Sequenom, San Diego, CA, USA) platform. The statistical analysis performed with Fisher's exact test showed no significant difference in frequencies of genotypes between both groups. The logistic regression showed that genotypes GT, TT and allele T were nonassociated with increased risk of asthenozoospermia in the patient group with ≤5% or >5% sperm with normal forms. The dependence on genotypes of semen parameters was further investigated in both patients and control group. There was no significant difference as compared to control group (P > 0.05). Our study indicated that eNOS gene G894T polymorphism may not have an adverse effect on semen parameters in a Chinese Han population.

Endothelial Nitric Oxide Synthase Gene Polymorphisms and Risk of Preeclampsia

Polymorphisms in endothelial nitric oxide synthase (eNOS) gene may affect the risk of preeclampsia. This systematic review aimed to provide an updated review of the literature to better understand the association between the eNOS gene polymorphisms and the risk of preeclampsia. We searched electronic databases of the human literature in PubMed, EMBASE, and the Cochrane Library up to July 2012. A meta-analysis was conducted on the association of eNOS G894T, T786C, and intron 4b/a polymorphisms with preeclampsia using (1) allele contrast, (2) recessive, (3) dominant, and (4) additive models. Thirty-three studies comprising 10,671 participants met the inclusion criteria. There was statistically significant association between the G894T variant and increased risk of preeclampsia (TT versus TG + GG: odds ratio 1.43, 95% confidence interval: 1.13 to 1.82). However, no significant risk of preeclampsia was observed either in the T786C or the intron 4b/a polymorphism. Homozygosity TT in eNOS G894T variant is significantly associated with an increased risk of preeclampsia.