Nitric Oxide Synthase Gene G894T Research Articles

The relationship between polymorphic variants of the endothelial NO-synthase gene and the course of diabetic nephropathy in patients with type 2 diabetes mellitus

Objective — to identify a possible association between the endothelial nitric oxide synthase (eNOS) gene G894T (rs1799983) polymorphism and the markers of renal function and glucose metabolism in patients with type 2 diabetes mellitus (DM2) with diabetic nephropathy (DN).
 Materials and methods. Examinations 126 patients with diabetic nephropathy (DN). The control group included 20 healthy individuals. Patients with DM2 were divided into two groups depending on the eNOS rs1799983 gene polymorphism: group I — patients with DN and G/G genotype eNOS G894T gene (n=80); group II — patients with DN and G/T and T/T genotypes eNOS G894T gene (n=46). Genotyping of the of the eNOS rs1799983 gene polymorphism was performed by the Taq‑Man® Fast Universal PCR Master Mix (Applied Biosystems, USA) and TaqMan® SNP Assay (Applied Biosystems, USA).
 Results. It has been established that in patients with DN, the distribution of genotypes of the G894T polymorphism of the eNOS gene corresponded to the Hardy‑Weinberg equilibrium in all groups and does not differ significantly from European populations. In diabetic patients with DN the 3 times higher total frequency of G/T and T/T genotypes eNOS G894T gene was established when compared to the control group. These findings prove the undoubted influence of the T allele on the development of DN in this group of patients. DN patients with genotypes G/T and T/T had significantly higher blood glucose and HOMA index (p <0.05) than G homozygotes (genotype G/G). Patients with DN and G/G genotype eNOS G894T gene had better glomerular filtration rate and lower albuminuria compared to patients with G/T and T/T genotypes (p <0.05).
 Conclusions. The establishing of association of eNOS gene polymorphism with the disease and further assessment of individual genetic risk is important for the development of a differentiated approach to the prevention and treatment of DN in patients with DM2 depending on the hereditary predisposition of an individual patient. Therefore, currently one of the most progressive approaches is to develop a strategy for early diagnosis, prognosis and preventive therapy of the disease using genetic markers.

The role of eNOS gene polymorphisms on contrast induced nephropathy development in chronic kidney disease patients.

Contrast nephropathy is a result of contrast media given through intravascular routes. Nitric oxide gene polymorphisms may alter the hemodynamic stability resulting in medullary ischemia Nitric oxide gene polymorphisms may have an enhancing role in contrast media related renal injury. The aim of this study was to investigate the role of eNOS intron 4a/b, T786C, and G894T gene polymorphisms on contrast-nephropathy risk. Ninety-four chronic kidney disease patients with contrast nephropathy and 120 chronic kidney disease patients without contrast nephropathy were included. DNA isolation was performed and specific regions of DNA for eNOS G894T, T786C, and intron 4a/b genes were amplified by polymerase chain reaction technique. TT polymorphism of T786C gene and GG polymorphism of G894T gene were detected to be possibly protective from contrast induced nephropathy. Endothelial nitric oxide synthase G894T gene polymorphisms, older age, and presence of diabetes mellitus may influence contrast nephropathy development.

Роль генетичних чинників у розвитку діабетичної дистальної симетричної полінейропатії (огляд літератури та власні дослідження)

У статті подані дані огляду літератури та власні спостереження з питання вивчення ролі генетичних чинників у ризику розвитку та прогресування тяжких ускладнень діабетичної дистальної симетричної полінейропатії. Встановлено, що у хворих із дистальною симетричною полінейропатією на тлі цукрового діабету типу 2 відзначається асоціація гомозиготного генотипу ТТ поліморфізму G894T гена ендотеліальної NO-синтази з вірогідно вираженими ознаками суб’єктивної симптоматики, наявністю аксонального ураження моторних нервів за електронейроміографічними параметрами, із зростанням рівня глікованого гемоглобіну, а також зі збільшенням вмісту продуктів пероксидного окиснення ліпідів.

Study of the Relation between Endothelial Nitric Oxide Synthase G894T Gene Variants and Occurrence of Type II Hepatorenal Syndrome

Background and study aim: The progress of hepatorenal syndrome (HRS) in hepatic patients is not yet understood. Nitric oxide level, through its impact on haemodynamic circulation, may be engaged in the progress of the disease. Our study expected to clarify the possible role of eNOS G894T in decompensated liver cirrhosis and HRS and its relationship with nitrite level. Methods: Study included 80 cirrhotic patients (40 decompensated cirrhotic and 40 HRS) and 40 healthy participants as controls. Renal and liver function tests, CBC, serum electrolytes, plasma nitrite and eNOS G894T by real-time PCR were surveyed. Results: There were higher frequencies of TT and GT genotypes of eNOS G894T versus GG in both cirrhotic (22.5% and 50% respectively) and HRS (30% and 45% respectively) than in controls (10% and 30%) (P=0.007). T allele was more prevalent than G allele in cirrhotic (47.5%) and HRS (52.5%) patients compared to controls (25.0%) (P=0.001). TT and GT genotypes increase risk of cirrhosis by OR 4.909 [95% CI: 1.24 – 19.46] and OR 3.636 [95% CI: 1.32 – 9.99] and HRS OR7.200 [95% CI: 1.86 – 27.77] and 3.600[95% CI: 1.27 – 10.7] respectively. T allele can increase risk of cirrhosis by OR 2.714 [95% CI: 1.39 – 5.30] and HRS OR 3.316 [95% CI: 1.70 – 6.48]. Clear connections were observed between TT genotype and lower plasma nitrite level (P<0.001). Conclusion: Mutant variants of eNOS G894T gene in cirrhotic and HRS patients from controls could partially explain the progress to decompensation and HRS in liver cirrhosis.

The endothelial nitric oxide synthase gene G894T, glutathione S-transferase (GSTM1 and GSTT1) polymorphisms as a risk factor in the patient with nephrolithiasis

BackgroundThe genetic features indicate a crucial role in nephrolithiasis. The present study was aimed to investigate the role of Glutathione-S-transferase Mu (GSTM1), Glutathione-S- transferase Theta (GSTT1) and endothelial nitric oxide synthase (eNOs) gene polymorphism in nephrolithiasis. MethodsWe involved a case-control study in which 480 individuals were divided into 240 healthy control and 240 patients with nephrolithiasis. For each patient and control, we measured biochemical criteria, levels of glutathione S-transferase, eNOs, GSTM1, GSTT1genes and eNOS genes polymorphism by PCR-RFLP. ResultsGSTM1 and GSTT1 null genotypes are not a risk features for nephrolithiasis. The eNOS frequency GG, GT, and TT genotypes by using Ban II enzyme as restriction enzyme were found to be (48.33, 36.67, and 15.00) %. The eNOS frequency TT, GT, and GG genotypes by using the Ban II enzyme as restriction enzyme were found to be 15.84, 25.83, and 58.33%, respectively. The result showed an increase in serum eNOs levels were in the patient's group comparing to control. ConclusionsThis work is the first in the literature to study the relation between eNOs genes polymorphisms and nephrolithiasis. The results conclude that TT genotypes in the eNOs genes are associated with an increase the oxidative stress in patients.

Association of endothelial nitric oxide synthase gene G894T polymorphism with blood oxygen transport

BackgroundNitric oxide (NO) is involved in formation of oxygen transport function of blood and oxygen transport in tissues by means of interaction with haemoglobin. Endothelial nitric oxide synthase gene G894T polymorphism affects the expression and the activity of the NO synthase enzyme. The influence of this polymorphism on the formation of oxygen-dependent processes in the body has not been completely investigated. ObjectiveTo evaluate the associations between G894T polymorphism of the endothelial nitric oxide synthase gene and the condition of oxygen transport function of blood in healthy male volunteers. MethodsThe study subjects were healthy young males aged 18–24 years (n = 165). The blood was drawn from the cubital vein at rest after 12 h following the last food intake. G984T polymorphism and the blood oxygen indices pO2, CvO2, SO2, pH, р50stand (the temperature was 37°С, рН = 7.4, рСО2 = 40 mm Hg) and р50act (actual temperature, рН and рСО2), etc. were determined. ResultsIn persons with the TT-genotype, the oxygen content in venous blood was 48.7% (q = 0.019) lower compared to subjects with the GT-genotype and 49.4% (q = 0.019) lower compared to subjects with the GG-genotype. The saturation of blood in carriers of the TT-genotype was 32.4% (q = 0.021) and 35.9% (q = 0.019) lower as opposed to subjects with the GT-genotype and the GG-genotype, respectively. In blood of subjects with the TT-genotype, the oxygen tension was 26.1% (q = 0.019) lower as compared to subjects with the GT-genotype and 27.4% (q = 0.019) lower as opposed to the GG-genotype. In turn, volunteers having a common allele in their genotype (GG + GT) demonstrated oxygen tension to be 26.7% (q = 0.019) higher compared to subjects with the TT-genotype. The blood pH values of the subjects having the recessive genotype were 0.022 units lower compared to the GG (q = 0.044) and GT (q = 0.042) genotypes. In volunteers with the TT-genotype, the p50stand parameter was 5.8% (q = 0.027) lower compared to subjects with the GT-genotype and 6.8% (q = 0.019) lower compared to volunteers with the GG-genotype. In persons with two T-alleles in their genotype, p50act was 5.4% (q = 0.019) lower compared to subjects with the GT-genotype and 6.4% (q = 0.019) lower compared to persons with the GG-genotype. ConclusionThe T-allele of G894T polymorphism is associated with low values for oxygen content, oxygen tension, acidic pH shift and increased haemoglobin affinity for oxygen under standard and real conditions. The presence of a minor allele in G894T polymorphism of the NOS3 gene contributes to formation of oxygen transport function of blood.

Prevalence of endothelial nitric oxide synthase (ENOS) gene G894T polymorphism and its association with hypertension: a population-based study with Brazilian women.

IntroductionHypertension is one of the most prevalent diseases in the world, accounting for millions of deaths each year. The reduction in the concentration of nitric oxide (NO) produced by the catalysis of endothelial nitric oxide synthase (eNOS) is associated with higher blood pressure (BP) levels. This reduction might be because of genetic polymorphisms. This study investigated the prevalence of the eNOS gene G894T polymorphism in women from northeast Brazil and its association with hypertension.Material and methodsThis cross-sectional study included 810 women (aged 19–49 years). Sociodemographic, health, anthropometric, and BP data were collected. Hypertension was defined according to the following criteria: systolic BP ≥ 140 mm Hg, diastolic BP ≥ 90 mm Hg, the regular use of antihypertensive medication, or some combination thereof. Epithelial cells from the cheek mucosa were obtained for DNA extraction. Genotyping was performed via real-time PCR. The measure of association was the prevalence ratio (PR) and its 95% CI as calculated via Poisson regression.ResultsThe frequencies of the GG, GT, and TT genotypes were 57.1%, 35.7%, and 7.2%, respectively. For each of these genotypes, the prevalence of hypertension in women was 17.9%, 23.6%, and 34.4%, respectively. Relative to the GG genotype, the PRs after adjusting for cofounding factors were 1.24 (95% CI: 0.95–1.61, p = 0.11) for GT and 1.76 (95% CI: 1.16–2.67, p < 0.01) for TT.ConclusionsThe T allele of the G894T polymorphisms is associated with hypertension in women. This may have implications for prevention and treatment.

An association between the endothelial nitric oxide synthase gene G894T polymorphism and premature coronary artery disease: a meta-analysis.

Previous epidemiological studies have suggested that genetic factors are more likely to influence the development of premature coronary artery disease (CAD) than disease in older patients. Several studies have evaluated the association between the G894T polymorphism located in an exon of endothelial nitric oxide synthase (eNOS) and the risk of premature CAD. However, the findings were inconsistent. Thus, we performed a meta-analysis to clarify the association; we conducted both overall and subgroup analyses. Odds ratios and 95% confidence interval were calculated to evaluate the association between the G894T polymorphism and the risk of premature CAD. Overall analysis revealed a significant association. Subgroup analysis in terms of ethnicity revealed a significant association, in all models evaluated, between the G894T polymorphism and susceptibility to premature CAD in mixed population. In contrast, no such association was evident in Caucasians and Asians. On further subgroup analysis based on the premature CAD subtypes, we found that the G894T polymorphism was correlated with premature myocardial infarction (MI) but not with premature CAD without MI. In conclusion, we confirmed that the eNOS G894T polymorphism is a risk factor for premature CAD, particularly in those suffering premature MI.

Heart failure and endothelial nitric oxide synthase G894T gene polymorphism frequency variations within ancestries

The G894T polymorphism in endothelial nitric oxide synthase enzyme gene plays an important role in heart failure (HF) and its frequency varies among populations. We investigated this association in highly admixed samples in terms of ancestry. The cohort included 210 HF patients and 106 healthy individuals. Self-reported race and NYHA class were analyzed for HF patients. G894T polymorphism was analyzed by polymerase chain reaction (PCR) and by restriction fragment length polymorphism technique. Ancestry was estimated using a PCR reaction containing 46 autosomal ancestry informative markers and an analysis by capillary electrophoresis. The GG homozygous genotype had a higher frequency in HF patients (63.8%) than in healthy individuals (48.1%), showing an increased chance (odds ratio 1.90, 95% confidence interval 1.18–3.05). The ancestry profiles in patients and controls were similar, with a major European contribution (57.1% and 63.2%), followed by African (30.2% and 24.0%) and Native American (12.7% and 12.8%), without a significant difference between both samples (p = 0.28). The GG genotype is associated to HF prognosis, and this association remains present in highly admixed sample groups.

Endothelial nitric oxide synthase gene G894T polymorphism and risk assessment for pregnancy-induced hypertension: evidence from 11 700 subjects

Recent studies have reported the association between endothelial nitric oxide synthase (eNOS) gene G894T polymorphism and pregnancy-induced hypertension (PIH). However, the results have been inconsistent. We conducted a comprehensive meta-analysis to explore this association. A total of 36 case-control studies involving 4028 PIH cases and 7672 controls were ultimately included. In the overall analysis, no association was identified between eNOS gene G894T polymorphism and PIH risk in any of the genetic models. In the subgroup analysis, the results showed that T-allele carriers had a higher risk of PIH than those with the G allele in Asians (G vs. T: odds ratio (OR)=0.76, 95% confidence interval (CI)=0.63-0.91, P=0.002; GT+TT vs. GG: OR=1.32, 95% CI=1.09-1.59, P=0.004; TT vs. GT+GG: OR=1.96, 95% CI=1.26-3.06, P=0.003; TT vs. GG: OR=1.99, 95% CI=1.27-3.11, P=0.003; GT vs. GG: OR=1.23, 95% CI=1.05-1.43, P=0.009). For Latin American and African populations, the association between G894T polymorphism and susceptibility to PIH was only observed in the dominant model. However, no association was observed in Europeans and Americans. Therefore, eNOS gene G894T polymorphism was related to PIH risk, especially for Asians.

Association between Endothelial nitric oxide synthase G894T gene polymorphism and risk of ischemic stroke in North Indian population: a case-control study

Background and purpose: Stroke is a multi-factorial disease influenced by both genetic and environmental factors. The aim of this case-control study was to determine the association between Endothelial Nitric Oxide Synthase G894T (rs1799983) gene polymorphism and susceptibility to ischemic stroke (IS) in North Indian population.Methods: In this present case-control study, genotyping was performed by using Polymerase chain reaction – Restriction fragment length polymorphism (PCR-RFLP) method for 250 IS patients and 250 age and sex matched controls. PCR results were confirmed by DNA sequencing. Frequency distribution of genotypes and alleles were compared between cases and controls using conditional logistic regression.Results: Hypertension, Diabetes, Dyslipidemia, Low Socioeconomic Status and Family History of Stroke were found to be independent risk factors for IS. Mean age of cases and controls were 52.83 ± 12.59 and 50.97 ± 12.70 years. Multivariate logistic regression analysis showed a significant association between eNOS G894T (rs1799983) polymorphism and risk of IS [OR = 1.57; 95%CI 1.05–2.37; p = 0.028] under dominant model. Based on Trial of Org 10172 in Acute Stroke Treatment classification, an independent association of large vessel disease (LVD) was observed with the risk of IS under the dominant [OR = 2.09; 95% CI 1.17–3.75; p = 0.01] and recessive [4.09 95% CI 1.06–15.68; p = 0.04] models. All the observed genotype frequencies were in accordance with the Hardy–Weinberg equilibrium (HWE) in both cases and controls.Conclusion: The findings of the present study suggest that polymorphism in G894T position of eNOS gene might be a risk factor for IS mainly for LVD stroke subtype in North Indian population. Further large prospective studies are required to confirm these findings.

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.

Association of endothelial nitric oxide synthase gene G894T polymorphism and serum nitric oxide levels in patients with preeclampsia and gestational hypertension

Objective: Pregnancy-induced hypertension is one of the most important cause of maternal-fetal morbidity and mortality. Pregnancy-related hypertensive disorders are usually associated with diminished nitric oxide (NO) levels. We aimed to evaluate the role of serum NO levels and eNOS gene G894T polymorphism on hypertensive disorders of pregnancy.Methods: Eighty patients with gestational hypertension or preeclampsia, and 80 healthy pregnants were enrolled to analyze serum NO levels and G894T polymorphism of the eNOS gene. NO level was analyzed by high-performance liquid chromatography (HPLC) method. The G894T polymorphism of the eNOS gene was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).Results: There was no significant difference between groups in terms of G894T/eNOS genotype and allele frequencies (p > 0.05). Serum NO levels were significantly lower in the patients group. In the control group, subjects with thymine-thymine (TT) genotype had significantly lower NO levels when compared to subjects with guanine-guanine (GG) or guanine-thymine (GT) genotype (p < 0.05).Conclusions: We failed to demonstrate an association between eNOS gene G894T polymorphism and serum NO levels in patients with pregnancy-induced hypertensive disorders. We established a relation between pregnancy-induced hypertension and low NO levels.

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.

Association of the endothelial nitric oxide synthase gene G894T polymorphism with the risk of diabetic nephropathy in Qassim region, Saudi Arabia—A pilot study

BackgroundDiabetic nephropathy (DN) is a chronic microangiopathic complication of type 2 diabetes mellitus (DM).Vascular endothelial dysfunction resulting from impaired nitric oxide synthase (NOS) activity in the vascular endothelial cells has been suggested as playing an important role in the pathogenesis of diabetic nephropathy (DN). Endothelial nitric oxide synthase (E-NOS) gene G894T polymorphism has been reported to be associated with endothelial dysfunction leading to DN.Our objective was to evaluate the association of G894T polymorphism of eNOS gene with the risk of DN among type 2 diabetic Saudi patients. MethodsOne hundred and twenty subjects were included in this study. They were divided into three groups. Group I, 40 controls. Group II, 40 type 2 diabetic patients without nephropathy. Group III, 40 type2 diabetic patients with nephropathy. Endothelial nitric oxide synthase (eNOS) G894Tpolymorphism was detected by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Plasma nitric oxide (NO) levels were estimated. ResultsE-NOS genotype frequency showed non-significant differences among the all studied groups (p>0.05). Both diabetic groups had significantly higher plasma nitrate levels than in controls with a significant increase in group III than in group II patients (all p<0.0001). E NOS 894TT genotype was associated with higher plasma nitrate levels in all groups. ConclusionE-NOS gene SNP is not considered as genetic risk factor for DN among type 2 diabetic Saudi patients. The higher plasma levels of nitrates as a marker of oxidative stress in diabetic patients with nephropathy suggest the possible role of oxidative stress but not e-NOS gene SNP in pathogenesis of the DN.

The association between endothelial nitric oxide synthase gene G894T polymorphism and hypertension in Han Chinese: a case-control study and an updated meta-analysis

Background: The G894T (rs1799983) polymorphism in endothelial nitric oxide synthase (eNOS/NOS3) gene has been implicated in susceptibility to essential hypertension (EH) in some studies, but no clear consensus has been reached in the Chinese population.Aims: This study aimed to investigate the association of the G894T polymorphism and EH in Han Chinese.Subjects and methods: First, a case-control study was performed involving 1525 subjects in northern Han Chinese to study the association between G894T variants and EH and then a meta-analysis was conducted of all available studies in Han Chinese. A total of 25 studies comprising 13 443 subjects were finally included in this meta-analysis.Results: The present case-control study failed to show significant association of G894T variant with EH in northern Han Chinese. The subsequent meta-analysis showed that this polymorphism might be associated with EH in Han Chinese (p < 0.001, OR = 1.32), especially in southern Han Chinese (p < 0.001, OR = 1.59), but not in northern Han Chinese (p = 0.12, OR = 1.16). The meta-regression analysis suggested that the geographic difference of subjects was related to heterogeneity (p = 0.029).Conclusions: The relationship between the G894T polymorphism and hypertension in Han Chinese may be attributed to the difference in geographic background of subjects. It is necessary to carry out further research with a large sample size and focusing on gene–environment interactions.

The association of endothelial nitric oxide synthase gene G894T polymorphism and serum nitric oxide concentration with microalbuminuria in patients with gestational diabetes

Gestational diabetes mellitus (GDM) is a glucose intolerant condition that affects 14% of all pregnancies. Diabetes mellitus (DM) occurs in 30 - 70% of patients with GDM after delivery. DM and GDM are associated with structural and functional deterioration of the renovascular system. Our aim is to investigate the association Glu- 298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene with serum nitric oxide levels and microalbuminuria in patients with GDM and healthy pregnancies. Serum nitric oxide (NO) levels, urinary excretion of albumin and Glu298Asp polymorphism of the eNOS gene were analyzed in 68 patients with GDM and 73 healthy controls. High performance liquid chromatography (HPLC-Griess) method was used to analyze serum NO levels. Microalbuminuria was evaluated by rate nephelometry method. The Glu298Asp polymorphism of the eNOS gene was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Nitric oxide, glucose, creatinine, and microalbuminuria were significantly different between the patients and the control subjects (p = 0.001, p = 0.001, p = 0.002, and p = 0.005, respectively). There was a significant difference between groups in terms of the ratio of GG/GT+TT of eNOS gene Glu- 298Asp (p = 0.02). The patients with GT+TT genotype had significantly higher microalbuminuria levels and lower NO concentrations (22.16 vs. 9.51, p = 0.005, and 10.56 vs. 12.73, p = 0.021, respectively). The presence of T allele of eNOS gene is an independent predictor of microalbuminuria (OR: 2.346, 95% confidence interval: 1.247 - 5.238, p = 0.02) as well as serum glucose and NO concentration. The G894T polymorphism of eNOS gene and decreased NO concentration seem to be independent predictors of increased urinary excretion of albumin in patients with GDM. Determining the frequency of eNOS gene G894T polymorphism may help to identify pregnancies at increased risk of microalbuminuria.

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.

Endothelial Nitric Oxide Synthase G894T Gene Polymorphism and Essential Hypertension in the Chinese Population: a Meta-Analysis Involving 11,248 Subjects

The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism has been suggested to be linked to the risk of essential hypertension (EH), however the results are still debatable. To assess the association between eNOS G894T gene polymorphism and EH, such electronic databases as Pubmed, Embase, Web of Science, China Biological Medicine Database (CBMD) and China National Knowledge Infrastructure (CNKI) were searched. The selection criteria were as follows: a) Evaluation of the association of eNOS G894T gene polymorphism and EH. b) EH diagnosis in compliance with EH diagnosis criteria of the World Health Organization (WHO) in 1999. c) The study results were in line with the Hardy-Weinberg equilibrium (HWE). In 23 separate studies with 11,248 subjects the relation between eNOS G894T gene polymorphism and EH was analyzed by current meta-analysis. Random effect model was used to calculate the pooled odds ratio (ORs) and its corresponding 95% confidence interval (95% CI). In this eNOS G894T gene polymorphism and EH meta-analysis in the Chinese population, the distribution of T allele frequency was 0.154 for EH group and 0.128 for the control group. A significant association was found between G894T gene polymorphism and EH (p=0.0007). The pooled OR for the distribution frequency of T allele was 1.33 (95% CI:1.13-1.56, P(heterogeneity) <0.00001). In the stratified analysis by ethnicity, there was a significant association in Han subgroup (p=0.005). The pooled OR for the distribution frequency of T allele was 1.31 (95% CI:1.09-1.59, P(heterogeneity) <0.00001). No significant increased risk for EH was found in the non-Han subgroup (p=0.08). In the current meta-analysis, T allele of eNOS G894T gene was suggested to be related to the increased risk of EH in the Chinese population, particularly in those of Han ethnicity.

Association Analysis of Endothelial Nitric Oxide Synthase G894T Gene Polymorphism and Erectile Dysfunction Complaints in a Population-Based Survey

Erectile dysfunction (ED) is a common disorder leading to a serious, negative impact on the quality of the patient's life. The gene encoding endothelial nitric oxide synthase (eNOS) is an interesting candidate gene for understanding the physiopathology of ED, as it is involved in the catalytic production of nitric oxide (NO), the neurotransmitter that plays a critical role in penile tumescence and erection. To evaluate a potential association between the G894T polymorphism in the eNOS gene and ED complaints in a population-based sample in São Paulo, Brazil. The prevalence of ED complaints was estimated according to the answer to the question "How would you describe your ability to get and keep an erection that is adequate for satisfactory intercourse?" ED was considered to be present if the response was "sometimes" or "never." A total of 449 men were enrolled in the study and answered an eight-item questionnaire to ascertain sexual performance/ED and satisfaction. The eNOS G894T polymorphism was genotyped using a standard polymerase chain reaction method. Univariate analysis demonstrated that ED was associated with diabetes, hypertension, sleep apnea severity, increasing age and body mass index, as well as testosterone levels (P < 0.05). Forward multiple regression models indicated that age was the only independent factor associated with ED in this population (odds ratio = 1.09; 95% CI 1.06-1.11; P < 0.0001). Genotypic and allelic analyses provided no evidence for an association between this polymorphism and the risk for ED complaints in this sample. Population stratification did not affect the association test results. This is the first study to examine the effect of polymorphisms in the eNOS gene and the risk for ED utilizing a case-control approach in the Brazilian population. Our results do not support a major role for eNOS gene polymorphisms in ED in this population.