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 endothelial nitric oxide synthase (Glu298Asp) gene polymorphism with radial artery spasm during cardiac catheterization in Egyptians

BackgroundNitric oxide (NO) exerts diverse effects on the cardiovascular system. Impairment of NO production plays a key role in cerebral and coronary artery spasm. We aimed to explore the predicting factors of radial artery spasm (RAS) and the association of eNOS gene polymorphism (Glu298Asp) with RAS during cardiac catheterization.Methods and results200 patients underwent elective coronary angiography through a trans-radial approach. The subjects were genotyped to the Glu298Asp polymorphism (rs1799983) on the eNOS gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results showed that the subjects with the TT genotype and T allele were significantly more likely to develop radial artery spasms (OR = 12.5, 4.6, P < 0.001 respectively). TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, radial tortuosity, and right radial access are independent predictors of radial spasm.ConclusionThe eNOS (Glu298Asp) gene polymorphism is associated with RAS during cardiac catheterization in Egyptians. TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, right radial access, and tortuosity are independent predictors of RAS during cardiac catheterization.

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 (&amp;gt;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&amp;lt;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 gene Glu298Asp variant confer risk in sudden sensorineural hearing loss

Background: Sudden sensorineural hearing loss (SSNHL) causes the loss of hearing of 30 dB or greater on at least three contiguous frequencies. It is known to be a multifactorial disease which the exact cause is unknown, rendering it as an idiopathic disorder of patients.Aims/objectives: This study aims to shed further light on pathogenesis of this disease by studying the association between eNOS gene Glu298Asp polymorphism and VDR gene FokI polymorphism with SSNHL in Iranian population.Material and methods: This study involves a total of 77 cases and 100 controls, with patients inflicted with SSNHL categorized in case group and healthy subjects as control group. Genotyping of the VDR and eNOS genes was conducted by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.Results: Our results showed a statistically significant association between genotype frequencies of eNOS gene Glu298Asp polymorphism in case group compared to healthy individuals in the control group (p = .01). Also, TT genotype was significantly the most prevalent genotype in case group in comparison to control group (TT vs GT + GG, OR = 3.5; 95% CI = 1.18–11.79). On the other hand, analysis of VDR gene FokI polymorphism frequencies showed no statistically significant association with SSNHL.Conclusions and significance: Our findings showed a significant association between the eNOS gene Glu298Asp polymorphism and SSNHL in the Iranian population; and “TT” genotype might be considered as a risk factor for SSNHL.

Endothelial Nitric Oxide Synthase (eNOS) Glu298Asp Gene Polymorphism (G894T) as a Risk Factor for Type 2 Diabetes Mellitus in the Tunisian Population

Introduction: Diabetes mellitus is a chronic disease whose global expansion gives it the characteristics of a pandemic. Diabetes risk factors are well known. In this work we proposed to study the role of genetic polymorphism of the eNOS G894T gene in the development of diabetes on the one hand and of these degenerative complications other. Methods: We conducted a prospective case-control study in which we included 200 subjects divided into 100 patients with type 2 diabetes and 100 controls in apparent good health. For each patient and control we measured lipid parameters, CRP-us and sought the G894T polymorphism of eNOS gene by PCR-RFLP. Results: The analysis of our results shows a statistically significant elevated TG values (p < 10﹣3), Lp (a) (p < 10﹣3), and CRP-us (p < 10﹣3) in type 2 diabetes compared with controls. The mutated genotypes of GT eNOS gene was significantly more frequent in diabetic patients. In our series, we did not notice any significant difference in genotype or allele frequency between diabetics with and without degenerative complications. Conclusion: The G894T polymorphism of eNOS gene appears to be a risk factor of T2DM. His role in the development of degenerative complications remains proved.

NOS3 gene Glu298Asp polymorphism and severity of disease in patients of ADPKD from North India

IntroductionGenetic modifying factors play a significant role in disease progression in autosomal dominant polycystic kidney disease (ADPKD). Identification of these factors could inform about targets for intervention. The present study investigates the role of Glu298Asp (c.894G>T) polymorphism of NOS3 gene in the progression of disease in ADPKD patients from North India, and compares with the results in studies among other ethnic groups. MethodsGenotyping for c.894G>T polymorphism was carried out in 123 patients of ADPKD and 100 healthy controls using polymerase chain reaction method. The allelic and genotypic frequencies of patients of ADPKD and healthy controls were analyzed using Chi-Square test. The mean age at onset of ESRD in the patients with PKD1 gene mutations, and in those with hypertension was correlated with G and T alleles of this polymorphism using Student's t-test. ResultsDistribution of GG, GT and TT genotypes were 0.73, 0.25 and 0.02 in patients of ADPKD and 0.67, 0.31 and 0.02 in healthy controls, respectively. The differences in the genotype frequencies between patients and controls were not significant (p=0.604). The frequency of mutant allele T of c.894G>T polymorphism did not vary significantly among patients of ADPKD with ESRD and those without ESRD (p=0.112). This polymorphism was also not associated with hypertension (p=0.681) and severity of disease in PKD1-linked patients (p=0.582). ConclusionsThe GT/TT genotype of c.894G>T (Glu298Asp) polymorphism did not have a significant role in modifying the progression of the disease in patients of ADPKD, or those with mutations in PKD1 gene from North India.

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.

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.

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 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.

OP-334 Association between Coronary No-Reflow Phenomenon and Endothelial Nitric Oxide Synthase (Glu298Asp) Gene Polymorphism

The aim of the present study was to demonstrate, through the analysis of novel parameter like PON1, that early changes in oxidative stress takes place in stable coronary artery disease (CAD) patients undergoing elective PCI with implantation of coronary stents. Methods: In this study 32 consecutive chronic stable angina patients (mean age 61 9.8 years, 75% male) undergoing PCI for management of single-vessel CAD (>70% stenosis in a major coronary artery) were included. PON1 enzyme activity were measured immediately before (t1) and just after the procedure (t2), as well as 24 hours later (t3), in order to serially evaluate the changes of oxidative stress parameters in PCI. Results: Baseline demographic, clinical and laboratorycharacteristics of the patients were demonstrated Table 1. When PON1 activities before (t1), immediately after (t2) and 24 hours after (t3) PCI procedurewere compared, a sustained decline was demonstrated (t3 t2 and t3, p 0.05, respectively). There was no correlation between serum PON1 activity and clinical and laboratory parameters of patients. Conclusion: We demonstrated, for the first time, that a substantial impairment of PON1 activity occurs after PCI in patients with stable CAD.We suggest that the PON1 assay may have the potential to be used as an early risk predictor for restenosis in patients undergoing elective PCI with implantation of BMS, a hypothesis which requires further 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.

Endothelial nitric oxide synthase (eNOS) gene Glu298Asp polymorphism and expression in North Indian preeclamptic women.

Pathophysiological processes in preeclampsia (PE) are influenced by genetic factors, nitric oxide synthases seem to play important roles, although their expression in and their role is still unclear. To better characterize the host genetic factors determining the susceptibility to PE, we evaluated the influence of polymorphisms (Glu298Asp) in the endothelial nitric oxide synthase (eNOS) gene on the risk of developing PE by checking the expression level. We conducted a hospital-based case-control study including 300 women with preeclampsia and 200 healthy pregnant women. Their blood samples were analyzed for levels of nitric oxide, eNOS gene polymorphism and expression. eNOS mRNA levels were determined using RT-PCR and expressed as arbitrary units after correction with control β-Actin gene mRNA levels. The mRNA expression of eNOS gene was found to be significantly lower in blood (P<0.05) from women with PE compared to that from normal pregnancies. The total nitric oxide levels (P<0.001) were decreased in study Group as compared to healthy pregnant patients. The intergenotypic variation of nitric oxide levels in preeclamptic women was found to be significant (P<0.001). These results indicate the relationship between reduced nitric oxide levels and eNOS gene polymorphism leading to its altered expression in preeclamptic women.

Association between Alzheimer's disease and the NOS3 gene Glu298Asp polymorphism

Background: The Glu298Asp gene polymorphism in NOS3 gene has been extensively investigated for association to Alzheimer's disease (AD), however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of NOS3 Glu298Asp polymorphism and AD risk by using meta-analysis. Methods: All eligible case–control studies were searched in PubMed and Embase. Odds ratios (OR) with the 95% confidence intervals (CI) were used to assess the association. Results: A total of 5522 cases and 4877 controls in 20 case–control studies were included. Obvious heterogeneity among studies was detected, and no significant association was observed between the NOS3 Glu298Asp polymorphism and AD risk. After exclusion of three studies, the heterogeneity disappeared and still no association was observed. In the subgroup analysis by ethnicity, we did not find any significant association between this polymorphism and AD risk in both Asians and Caucasians. Conclusions: This meta-analysis suggested that the NOS3 Glu298Asp gene polymorphism is not a strong risk factor for AD. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of NOS3 gene and AD risk, more studies with large groups of patients are required.

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.

Possible Relation between the NOS3 Gene GLU298ASP Polymorphism and Bladder Cancer in Turkey

Endothelial nitric oxide synthase (eNOS), encoded by the NOS3 gene, has been suggested to play an important role in uncontrolled cell growth in several cancer types. The objective of this study was to evaluate the role of the NOS3 Glu298Asp polymorphism in bladder cancer susceptibility in a Turkish population. We determined the genotypes of 66 bladder cancer cases and 88 healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. A significant association for NOS3 Glu298Asp heterozygotes genotypes and T allely were found between healthy controls and bladder cancer, respectively (p<0.001: p=0.002). There were no significant associations between any genotypes and the stage, grade, and histological type of bladder cancer. Our study suggested an increased risk role of NOS3 GT genotype in bladder cancer susceptibility in our Turkish population.

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.

Correlation of Glu298Asp eNOS Polymorphism with Serum NO Levels in Egyptian Patients with Coronary Artery Disease

Background: Nitric oxide (NO) is a potent vasodilator synthesized by the vascular endothelium. It has been reported that endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphism is associated withcoronary artery disease (CAD). Methodology: In this study, we investigated Glu298Asp eNOS polymorphism and serum NO in a group of 146 age-matched male subjects; 77 patients with coronary artery disease (CAD) classified according to the severity of coronary insufficiency and 69 normal male controls. Results: The obtained frequencies of the eNOS Glu298Asp genotypes for the CAD subjects were GG (54.5%), GT (31.20%), and TT (14.3%).The allele distributions of G and T were 70.1 and 29.9%, respectively. In the control group, the genotype frequencies were 53.6% for GG, 36.2% for GT, and 10.2% for TT, and the frequencies of the G and T alleles were 71.7% and 28.3%, respectively. There we re no significant differences in genotype and allele frequencies between the CAD patients and the control group. The mean serum NO levels in CAD patients was significantly higher than that of healthy subjects (p=0.0139). Conclusion: No significant associa tion was detected when CAD severity, genotypes and NO serum levels were correlated.