Nitric Oxide Synthase Polymorphisms Research Articles

Combined effects of cigarette smoking, alcohol drinking and eNOS Glu298Asp polymorphism on blood pressure in Chinese male hypertensive subjects.

INTRODUCTIONGenetic factors and lifestyle exposures, as well as their combinations, play important roles in the development of hypertension. We examined whether cigarette smoking, alcohol drinking and the Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene generate combined effects on blood pressure (BP) in hypertensive subjects.METHODSA total of 342 essential hypertensive subjects were recruited from Susong community in Anhui province, China, from July 2017 to January 2018, and the plasma biochemical parameters and the genotype on Glu298Asp polymorphism were determined.RESULTSThere were no gender differences in the distributions of alleles and genotypes in hypertensive subjects. The proportions of cigarette smoking and alcohol drinking in male hypertensive subjects were remarkably higher than those in the females (p<0.001). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels of mutant genotypes (Glu/Asp and Asp/Asp) were significantly higher than those of wild genotype (Glu/Glu) (p=0.013 and 0.026, respectively) in male hypertensive subjects. Moreover, the SBP and DBP levels of the mutant genotype were remarkably higher than those of wild genotype in both cigarette smoking and alcohol drinking male hypertensive subjects (p=0.034 and 0.043, respectively).CONCLUSIONSCigarette smoking, alcohol drinking and the Glu298Asp polymorphism of the eNOS gene generate combined effects that increase the susceptibility of the mutant genotype to BP in Chinese male hypertensive subjects.

Short-term clinical outcomes in patients with acute myocardial infarction after successful percutaneous coronary revascularization: the role of promoter polymorphism of the endothelial nitric oxide synthase gene

Background: The purpose of this study was to investigate the associations between variants of a promoter polymorphism of the endothelial nitric oxide synthase (eNOS) gene and clinical outcomes in acute ST-segment elevation myocardial infarction (STEMI) patients after a successful primary percutaneous coronary artery intervention (PCI).&#x0D; Methods: 177 patients with acute STEMI, 82 patients with angiographically proven stable coronary artery disease, and healthy volunteers were included in the study. The primary end-point was a combined event (follow-up major adverse cardiac events –MACEs and hospitalization) that occurred within 6-month of the discharge from the hospital.&#x0D; Results: The combined end-point was determined in 72 patients from the entire acute STEMI population (40.6%), including 24 events for 786TT genotype, 23 events for 786TC genotype and 25 events for 786CC genotype. Kaplan-Meier curves demonstrated that acute STEMI patients with 786CC eNOs genotype had lower MACEs free accumulation when compared to those with 786TC and 786TT eNOs genotypes at 6-month follow up period (Log-rank p &lt; 0.001). Multivariate Cox regression analyses identified 786CC in eNOs gene as an independent predictor of clinical outcomes in STEMI after PCI.&#x0D; Conclusions: the 786CC polymorphism in eNOs gene is an independent predictor for clinical outcomes after a successful primary PCI in acute STEMI.&#x0D;

The VNTR polymorphism of the endothelial nitric oxide synthase gene and blood pressure in women at the end of pregnancy

ObjectiveExamine the association of the 4a/4b polymorphism of endothelial nitric oxide synthase (eNOS) with blood pressure in women at late pregnancy. Materials and methodsBlood pressure before pregnancy and at the end of gestation (37–40-week term) was measured in 588 women of the Russian ancestry. The women were divided into groups according to the body mass index and the presence of preeclampsia at late pregnancy. The 4a/4b polymorphism of the eNOS gene was genotyped using PCR with subsequent screening of amplified fragment length polymorphisms. ResultsThe 4a4a eNOS genotype was associated with higher levels of diastolic blood pressure in pregnant women and with more pronounced dynamics of the diastolic and mean arterial pressure in the development of pregnancy (p = 0.02–0.03). Pregnant women with the 4a4a genotype and increased body mass index had higher systolic, diastolic, and mean arterial pressure (p = 0.001–0.009). In pregnant women with preeclampsia, the 4a4a genotype was associated with higher level of diastolic blood pressure at the end of pregnancy (p = 0.04), whereas in the women without preeclampsia this genotype was associated with more pronounced changes of blood pressure at pregnancy (p = 0.02). ConclusionThe results of our study suggest that the genotype 4a4a of the eNOS gene is associated with higher levels of blood pressure in women at the end of pregnancy.

Role of Endothelial Nitric Oxide Synthase Polymorphisms in Atrial Fibrillation: A PRISMA-Compliant Meta-Analysis

BackgroundResearch interest in endothelial nitric oxide synthase(eNOS) polymorphisms and atrial fibrillation (AF) has grown in last recent years, but the results of individual studies are inconsistent due to their small sample sizes.Material/MethodsWe searched databases for eligible studies on eNOS and AF, extracted the relevant data, and rigorously screened them according to inclusion and exclusion criteria. Then, we evaluated the study quality according to the Newcastle-Ottawa scale score, and we pooled the odds ratios (ORs) and 95% confidence intervals (CIs) by using a random-effects model or fixed-effects model based on inter-study heterogeneity. In addition, we performed subgroup analysis and sensitivity analysis and assessed publication bias.ResultsAccording to the inclusion and exclusion criteria, we finally found 8 studies in this search. The recessive (OR=0.81; 95% CI=0.67 to 0.97; p=0.988; I2=0.0%) model showed that the eNOS 786T/C polymorphism was relevant to AF. We also found that the eNOS 786T/C polymorphism decreases the risk of AF, especially in white people (OR=0.81; 95% CI=0.67 to 0.97; P=0.023 for recessive model) and in the control population (OR=0.79; 95% CI=0.65 to 0.97; P=0.022 for recessive model). We found no obvious publication bias.ConclusionsThe eNOS gene loci 786T/C polymorphism is relevant to the risk of AF. Our results suggest that the 786T/C polymorphism significantly decreases AF risks in white people and control populations. Larger studies are required for further evaluation.

Impact of endothelial nitric oxide synthase polymorphisms on urothelial cell carcinoma development

ObjectivesUrothelial cell carcinoma (UCC), a major malignancy of the genitourinary tract, is induced through carcinogenic etiological factors. Endothelial nitric oxide synthase (eNOS) is one of the major isoforms of nitric oxide synthase and is involved in various pathophysiologic and physiologic processes. In this study, eNOS single-nucleotide polymorphisms were investigated to evaluate UCC susceptibility and clinicopathological characteristics. Materials and methodsTwo single-nucleotide polymorphisms of eNOS in 431 patients with UCC and 862 controls without cancer were analyzed using real-time polymerase chain reaction. ResultsThe results showed that 272 men with UCC having eNOS 894 G > T rs1799983 “GT + TT” variants had a high risk of developing a large tumor (T1–T4, P = 0.038). Furthermore, a correlation was observed between the expressions of eNOS and invasive tumor, metastasis and poor survival in urothelial carcinoma in The Cancer Genome Atlas data set. ConclusionOur results indicated that male patients with UCC carrying eNOS 894 G > T rs1799983 “GT + TT” genetic variants have a high risk of developing a large tumor, and eNOS polymorphisms may serve as a marker or therapeutic target in UCC treatment.

The Correlation of Endothelial Nitric Oxide Synthase (eNOS) Polymorphism and Other Risk Factors with Aneurysmal Subarachnoid Hemorrhage: A Case-Control Study.

Endothelial nitric oxide synthase gene (eNOS) polymorphism is an association with cerebral aneurysm formation, rupture, and vasospasm and plays a role in the a functional outcome. The aim of the study was to evaluate the role of eNOS gene polymorphism and further assess the predictors of outcome in the aneurysmal subarachnoid hemorrhage (aSAH). A prospective case-control study was conducted from 2009 to 2012 among those who presented with aSAH. A serum sample was collected from aSAH patients along with age and sex-matched healthy controls. The frequency of polymorphism of eNOS gene and other factors (demographic and aneurysmal) were correlated with functional outcome at six month of follow-up. 100 patients with aSAH and 100 healthy controls were enrolled in the cohort. The mean age of the patient group was 51.61 years and control group was 45.81 years with a male:female ratio of 1:1.38 and 1:1.08 for patients and controls, respectively. Among all eNOS polymorphisms, 4BB (65%) 24-VNTR, TT (71%) of T-786C, and GG (71%) of G947T were the most common and frequency was similar in the control group. The occurrences of hypertension, smoking, diabetes were 32%, 37%, and 7% respectively in the patient group. Maximum patients were in WFNS grade 1 (53%) followed by 23% grade 2 and only 10% in grade 4. Fisher grade 3 (57%) was the most common followed by Fisher grade 4 (28%). Most aneurysms (97%) were in anterior circulation. 83% of the aneurysms were clipped and 10% underwent coiling. Size-wise most of the aneurysms were in the middle group (6-9 mm) followed by bigger group (>10 mm) (37%); only 6% aneurysms were in the small aneurysm (<6 mm) group. 33% of the patients had evidence of vasospasm. TT of G894T polymorphism (60%) had the highest incidence of vasospasm. Univariate analysis showed smoking (OR: 3.19, CI: 1.19-8.84, P = 0.01), 4AA (OR: 12.15, CI: 1.13-624.9, P = 0.03) variety of 24-VNTR polymorphism, CC (OR: 15.39, CI: 1.60-762.8, P = 0.01) variety of T786C polymorphism, Fisher grade 4 (OR: 3.43, CI: 1.24-9.68, P = 0.01), WFNS grade (poor vs. good) (OR: 3.42, CI: 1.17-10.12, P = 0.02), vasospasm (OR: 3.84, CI: 1.42-10.75, P = 0.006), intraoperative rupture (OR: 4.77, CI: 1.55-15.27, P = 0.004) were significantly related with unfavorable outcome at 6 months follow-up. In regression analysis, smoking (CI: 0.06-0.69, P = 0.01), Fisher grade 4 (CI: 0.09-1.00, P = 0.05), and intraoperative rupture (CI: 0.05-0.89, P = 0.03) were correlated with an unfavorable outcome at 6 months follow-up. The eNOS gene polymorphism, smoking, clinical grade (WFNS), Fisher grade, intraoperative rupture, and vasospasm play a role in functional outcome after the treatment of cerebral aneurysms.

Effects of eNOS gene polymorphisms on individual susceptibility to cancer: A meta-analysis

BackgroundWhether endothelial nitric oxide synthase (eNOS) polymorphisms are implicated in cancer development remains controversial. Therefore, we performed this study to obtain a more conclusive result on associations between eNOS polymorphisms and cancer. MethodsLiterature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. ResultsForty-one studies were enrolled for analyses. Pooled overall analyses showed that rs1799983 (dominant model: p = 0.01; recessive model: p = 0.007; allele model: p = 0.005), rs2070744 (recessive model: p = 0.004) and rs869109213 (recessive model: p < 0.0001; allele model: p = 0.02) polymorphisms were all significantly associated with individual susceptibility to cancer. Further subgroup analyses revealed that rs2070744 and rs869109213 polymorphisms were only significantly associated with individual susceptibility to cancer in Caucasians, whereas the rs1799983 polymorphism was significantly associated with individual susceptibility to cancer in both Caucasians and Asians. ConclusionsOur findings indicated that rs1799983, rs2070744 and rs869109213 polymorphisms may serve as genetic biomarkers of cancer in certain ethnicities.

Associations between endothelial nitric oxide synthase gene polymorphisms and the risk of coronary artery disease: A systematic review and meta-analysis of 132 case-control studies.

The roles of endothelial nitric oxide synthase gene polymorphisms in coronary artery disease have been intensively analyzed, with inconsistent results. Therefore, we performed this study to better assess the relationship between endothelial nitric oxide synthase genetic variations and the risk of coronary artery disease. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios with 95% confidence intervals were used to evaluate associations between endothelial nitric oxide synthase polymorphisms and coronary artery disease. A total of 132 genetic association studies were finally included. Significant associations with the risk of coronary artery disease were detected for the rs891512, rs1799983, rs2070744, rs11771443 and rs869109213 polymorphisms. Further subgroup analyses according to ethnicity of participants revealed that the rs1799983 and rs2070744 polymorphisms were significantly associated with the risk of coronary artery disease in both Caucasians and Asians, whereas the rs869109213 polymorphism was only associated with the risk of coronary artery disease in Caucasians. When we stratified data based on type of disease, we found that the rs1799983, rs2070744 and rs869109213 polymorphisms were all significantly correlated with the risk of myocardial infarction or acute coronary syndrome in certain genetic models. In conclusion, our findings indicate that the rs891512, rs1799983, rs2070744, rs11771443 and rs869109213 polymorphisms may serve as genetic biomarkers of coronary artery disease.

Pharmacogenetic relevance of endothelial nitric oxide synthase polymorphisms and gene interactions.

Endothelial nitric oxide synthase (NOS3) is a key enzyme responsible for nitric oxide (NO) generation in the vascular endothelium. Endothelial dysfunction is characterized by reduced NO production, and is a hallmark of cardiovascular diseases. Drugs with cardiovascular action may activate NOS3 and result in NO release and vasodilation. Moreover, genetic variations affect NOS3 expression and activity, and may partially explain the variability in the responses to cardiovascular drugs. We reviewed NO signaling and genetic effects on NO formation, and the effects of NOS3 polymorphisms, haplotypes and gene-gene interactions within NO signaling pathways on the responses to cardiovascular drugs. We discuss the role of rare NOS3 variants and further gene-gene interactions analysis for the development of novel therapies for cardiovascular diseases.

Genetic associations of bradykinin type 2 receptor, alpha-adrenoceptors and endothelial nitric oxide synthase with blood pressure and left ventricular mass in outpatients without overt heart disease

BackgroundPhysiological pathways such as bradykinin, renin-angiotensin, neurohormones and nitric oxide have been shown to play an important role in the regulation of cardiovascular function. Genetic variants of these pathways may impact blood pressure and left ventricular (LV) mass in different populations. To evaluate associations of genetic polymorphisms of bradykinin B2 receptor (BDKRB2), alpha-adrenergic receptors (ADRA) and endothelial nitric oxide synthase (eNOS) on the modulation of the blood pressure and the left ventricular mass. MethodsWe enrolled 758 individuals without overt heart disease. Blood pressure was estimated by auscultatory method during the clinical examination. Left ventricular (LV) mass was assessed by echocardiography. Genotypes for ADRA1A rs1048101, ADRA2A rs553668, ADRA2B rs28365031, eNOS rs2070744, eNOS rs1799983, and BDKRB2 rs5810761 polymorphisms were assessed by high-resolution melting analysis. ResultsBDKRB2 polymorphism rs5810761 was associated with blood pressure. Carriers of DD genotype had higher levels of SBP and DBP than carrier of II genotype (p = 0.013 and p = 0.007, respectively). eNOS polymorphism rs1799983 was associated with DBP. Carriers of GT genotype had lower levels of DBP than carriers of GG genotype (p = 0.018). eNOS polymorphism rs2070744 was associated with LV mass. Carriers of TC genotype had higher LV mass than carriers of TT genotype (p = 0.028). ConclusionsIn a cohort of individuals without overt heart disease, the BDKRB2 rs5810761 polymorphism (DD genotype carriers) were associated higher systolic and diastolic blood pressures, and the eNOS rs1799983 polymorphism (T allele carriers) were associated with lower diastolic blood pressure. The eNOS rs2070744 polymorphism (C allele carriers) was associated with higher left ventricular mass. These data suggest that eNOS and bradykinin receptor genetic variants may be potential markers of common cardiovascular phenotypes.

Polymorphisms of endothelial nitric oxide synthase and hypoxia-inducible factor 1 alpha genes play a role in susceptibility to coronary artery disease

Objective: Genetics is a known factor in the susceptibility to cardiovascular disease. In this study, polymorphisms of endothelial nitric oxide synthase (eNOS) (T876C and G894T) and hypoxiainducible factor 1 (HIF1) (rs10873142 and rs41508050) in coronary artery disease were compared with healthy subjects, and the relationship between these mutations and risk of coronary artery disease (CAD) was assessed.&#x0D; Methods: Blood samples were collected from 138 patients with obstructive CAD and 115 healthy subjects. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), Griess test, and enzyme-linked immunosorbent assay (ELISA) were used to measure serum nitric oxide (NO) and paraoxonase antioxidant. Independent t-test was used to examine the relationship between variables.&#x0D; Results: There was no significant difference between genotype frequency in healthy subjects and patients for eNOS and HIF1 alpha polymorphisms. There was no significant difference between these polymorphisms and age, sex, hypertension and lipidemia. Furthermore, the difference in mean serum levels of NO in different genotypes of the G894T gene was not significant between the patient and control groups. However, the difference in mean serum NO levels in different genotypes of the T786C gene was significant between the patient and control groups such that minimum and maximum serum NO levels were observed in individuals bearing TT and TC genotypes, respectively. The difference in mean serum NO levels was higher in patients than in controls, and was statistically significant.&#x0D; Conclusions: The results suggest that the T876C polymorphism could be associated with low serum NO level and implicated as a risk factor for developing CAD. Furthermore, our findings indicate that genetics may not be involved in susceptibility to CAD; however, further comprehensive studies are required.

Endothelial nitric oxide synthase (−786T&gt;C) polymorphism and migraine susceptibility

Background:The aim of this study was to evaluate the correlation between endothelial nitric oxide synthase (eNOS) polymorphism (−786T>C) and migraine susceptibility in a meta-analysis.Methods:A literature search was performed for case–control studies from inception to July 30, 2018 focusing on eNOS polymorphism (−786T>C) and risk of migraine. From 454 full-text articles, 6 were included in this study. Heterogeneity was assessed with the I2 index and quality assessment was performed using the Newcastle–Ottawa scale.Results:CC genotype was not related to higher susceptibility of migraine compared with TT+ TC genotypes with significant difference (fixed effects model; OR = 1.27; 95% CI = 0.90–1.80; P = .17; I2 = 18%). However, subgroup analysis showed CC variant increase the risk for migraine compared with TT+ TC genotypes in Caucasian populations (fixed effects model; OR = 1.62; 95% CI = 1.03–2.56; P = .04; I2 = 18%), which could not be observed in non-Caucasian populations (fixed effects model; OR = 0.88; 95% CI = 0.51–1.53; P = .66; I2 = 0%). There was no significant difference for other genotypes and alleles between patients with migraine and healthy controls (all P > .05).Conclusion:This meta-analysis indicated that CC variant increases the risk for migraine compared with TT + TC genotypes in Caucasian populations.

The correlation between gene polymorphisms of endothelial nitric oxide synthase and aneurismal subarachnoid hemorrhage.

To discuss the association of the T786C and G894T polymorphisms of endothelial nitric oxide synthase (eNOS) with the occurrence and prognosis of aneurismal subarachnoid hemorrhage (aSAH). One hundred sixty-nine patients with aSAH were collected as the case group, which was divided into the good prognosis group and adverse prognosis group according to the condition 3months after the treatment. One hundred fifty-six healthy volunteers were collected as the control group. The allele and genotype of T786C and G894T polymorphisms of eNOS were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype and allele frequency of eNOS were compared between different groups. And then, the risk factors of aSAH occurrence and prognosis were analyzed by using the logistic regression model. Both the genotype and allele frequency distributions of T786C and G894T between the case group and control group were significantly different (P < 0.05). There were significant differences in the distribution of G894T and T786C allele frequency and G894T genotype between the good prognosis group and adverse prognosis group, and there was no difference in T786C genotype. The results of the logistic regression analysis indicated that T786C and G894T polymorphisms of eNOS were independent influencing factors on the occurrence of aSAH and the G894T polymorphism was also closely related to the prognosis. T786C and G894T polymorphisms of eNOS gene were correlated with the occurrence and prognosis of aSAH, and the G894T polymorphism might be an independent influencing factor.

Endothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients.

The biological mechanisms behind the development of pulmonary hypertension in the setting of left heart failure (HF-PH), including combined pre- and post-capillary pulmonary hypertension (Cpc-PH), remains unclear. This study aimed to use candidate polymorphisms in nitric oxide synthase (NOS) genes to explore the role of NOS in HF-PH. DNA samples from 118 patients with HF-PH were genotyped for the NOS3 rs1799983 and NOS2 rs3730017 polymorphisms. A multiple regression model was used to compare hemodynamic measurements between genotype groups. Patients with the T/T genotype at rs1799983 possessed a nearly 10 mmHg increased transpulmonary gradient (TPG) compared to those with other genotypes (P = 0.006). This finding was replicated in an independent cohort of 94 HF-PH patients (P = 0.005). However, when tested in a cohort of 162 pre-capillary pulmonary arterial hypertension patients, no association was observed. In a combined analysis of both HF-PH cohorts, mean pulmonary artery pressure (mPAP), diastolic pulmonary gradient (DPG), and CpcPH status were also associated with rs1799983 genotype (P = 0.005, P = 0.03, and P = 0.02, respectively). In patients with HF-PH, the NOS3 rs1799983 polymorphism is associated with TPG, and potentially mPAP and DPG as well. These findings suggest that endothelial NOS (encoded by NOS3) may be involved in the pulmonary vascular remodeling observed in Cpc-PH and warrants further study.

Prevalence of common polymorphisms of AT-rich interaction domain 1A and endothelial nitric oxide synthase in patients with endometriosis compared to control group

Introduction: Endometriosis is a common gynecologic disorder defined as ectopic presence of endometrial tissue in extrauterine sites. Endometriosis is associated with infertility and risk of malignancy. Identification of genetic factors responsible for development and malignant transformation of endometriosis can improve therapeutic approaches. In this study, we investigated the association of AT-rich interaction domain 1A ( ARID1A) and endothelial nitric oxide synthase ( eNOS) polymorphisms with endometriosis and staging of the disease. Methods: A total of 100 women with laparoscopy-confirmed diagnosis of endometriosis were included and compared with 100 women without endometriosis as the control group. Genotypes of patients regarding Gln920Ter polymorphism of ARID1A gene and Glu298Asp polymorphism of eNOS gene were determined by polymerase chain reaction techniques on blood samples from the study population. The prevalence of each genotype in endometriosis patients was compared with healthy controls using the chi-square test. Results: Significantly higher prevalence of non-CC genotype for ARID1A Gln920Ter polymorphism and non-GG genotype for G894T polymorphism of the eNOS gene was detected in the endometriosis group. There was no significant relationship between these polymorphisms and staging of endometriosis. Discussion: Significant variation of prevalence of Gln920Ter polymorphism of the ARID1A gene and Glu298Asp polymorphism of the eNOS gene among the two groups can indicate a causative effect of these genetic alterations on the development of endometriosis.

Endothelial nitric oxide synthase polymorphisms affect the changes in blood pressure and nitric oxide bioavailability induced by propofol

Propofol anesthesia is usually accompanied by hypotension, which is at least in part related to enhanced endothelial nitric oxide synthase (NOS3)-derived NO bioavailability. We examined here whether NOS3 polymorphisms (rs2070744, 4b/4a VNTR, rs3918226 and rs1799983) and haplotypes affect the changes in blood pressure and NO bioavailability induced by propofol. Venous blood samples were collected from 168 patients at baseline and after 10 min of anesthesia with propofol 2 mg/kg administered intravenously by bolus injection. Genotypes were determined by polymerase chain reaction and haplotype frequencies were estimated. Nitrite concentrations were measured by using an ozone-based chemiluminescence assay, while NOx (nitrites + nitrates) levels were determined by using the Griess reaction. We found that CT + TT genotypes for the rs3918226 polymorphism, the ba + aa genotypes for the 4b/4a VNTR and the CTbT haplotype were associated with lower decreases in blood pressure and lower increases in nitrite levels after propofol anesthesia. On the other hand, the TCbT and CCbT haplotypes were associated with more intense decreases in blood pressure and higher increases in nitrite levels in response to propofol. Our results suggest that NOS3 polymorphisms and haplotypes influence the hypotensive responses to propofol, possibly by affecting NO bioavailability.

Association of endothelial nitric oxide synthase (eNOS) polymorphisms with EGFR-mutated lung adenocarcinoma in Taiwan.

EGFR mutation of Non-small cell lung cancers (NSCLC) was predominantly seen in Asian population and it was considered as a predictor of responsiveness. Eendothelial nitric oxide synthase (eNOS) plays a vital role in chronic inflammation and carcinogenesis. In this study, we aimed to explore the association between the genetic polymorphisms of eNOS (-786T/C and 894 G/T) and EGFR mutation in patients with lung adenocarcinoma. A total of 277 patients with diagnosed lung adenocarcinoma were recruited between years 2012 and 2015. All study subjects underwent the analysis of eNOS genetic variants (-786 T/C and 894 G/T) using real-time polymerase chain reaction (PCR) genotyping. Our results showed that, among the 277 patients, variant types (GT + TT) of eNOS 894 G/T polymorphism were significantly positively correlated with EGFR mutation type, specifically exon 19 in-frame deletion. With the subgroup of EGFR L858R mutation, variant genotypes (GT + TT) of eNOS 894 G/T were significantly associated with lymph node invasion. Moreover, in silico analysis indicated that eNOS 894 G/T altered the eNOS expression. In conclusion, our study showed that eNOS 894 G/T variants were significantly associated with EGFR mutation types of lung adenocarcinoma, specifically exon 19 in-frame deletion. This may be utilized as a prediction of tumor invasiveness and therapy responsiveness.

Distinct role of endothelial nitric oxide synthase gene polymorphisms from menopausal status in the patients with sporadic breast cancer in Taiwan

Breast cancer has a high incidence in Taiwanese women and worldwide. Previous studies have indicated that NO has multiple independent roles in carcinogenesis; genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) gene could modify its transcription and endogenous NO production. Previous studies have reported conflicting results for the relationship between polymorphisms in the eNOS gene and breast cancer risk. Estrogen levels are associated with eNOS expression; accordingly, variation in estrogen levels may contribute to the discordant results. Therefore, in this study, the effects of eNOS polymorphisms on breast cancer susceptibility were examined in terms of menopausal status in Taiwanese women. Three eNOS polymorphisms (−786T > C, VNTR, and 894G > T) were genotyped in 283 patients with breast cancer (139 premenopausal and 144 postmenopausal) and 200 cancer-free controls (100 premenopausal and 100 postmenopausal) by PCR-RFLP. There was a significantly higher breast cancer risk in premenopausal women carrying 894G > T T than in those with the 894G > T GG genotype; however, postmenopausal women carrying 894G > T T had a lower risk of developing breast cancer. In addition, based on a binary logistic regression analysis, interaction effects of these polymorphisms differed according to menopausal status. The relationship between eNOS polymorphisms and breast cancer hazard depended on menopause status, especially for the 894G > T polymorphism, which may provide an explanation for previous conflicting results.

The role of endothelial nitric oxide synthase −786 T/C polymorphism in cardiac instability following aneurysmal subarachnoid hemorrhage

IntroductionCardiac abnormalities are observed frequently after aneurysmal subarachnoid hemorrhage (aSAH). A subset of aSAH patients develops neurogenic cardiomyopathy, likely induced by catecholamine excess. Genetic polymorphisms of the endothelial nitric oxide synthase (eNOS) gene have been linked to decreased nitric oxide (NO) levels, coronary artery spasm, and myocardial infarction. The role of the eNOS single nucleotide polymorphism (SNP) −786 T/C in cardiac instability following aSAH has not been previously investigated. MethodsFrom 2012 to 2015, aSAH patients were prospectively enrolled in the Cerebral Aneurysm Renin Angiotensin System (CARAS) study at two academic institutions. Blood samples were used to assess the eNOS SNP -786 T/C rs2070744 through 5'exonuclease (Taqman) genotyping assays. Associations between this polymorphism and cardiac instability following aSAH were analyzed. ResultsMultivariable analysis demonstrated a dominant effect of the C allele of eNOS SNP -786 T/C on cardiac instability in patients with aSAH. A lower Glasgow Coma Scale score and a history of ischemic vascular disease were also associated with cardiac instability. Furthermore, cardiac instability independently predicted poor functional outcome upon discharge from the hospital. ConclusionsThe C allele of the eNOS SNP -786 T/C was independently associated with an increased risk for cardiac instability following aSAH. Cardiac instability itself was a risk factor for an unfavorable functional outcome upon discharge from the hospital.

Endothelial nitric oxide synthase genepolymorphisms in patients with slowcoronary flow.

Background and aimsThe aim of this study was to explore potential associations of the intron 4 variable number of tandem repeats (VNTR) and E298A polymorphisms of the endothelial nitric oxide synthase (eNOS) gene with slow coronary flow (SCF). The association between plasma nitrate and nitrite (NOx) concentrations and eNOS gene polymorphisms was also assessed.Materials and methodsThe intron 4 VNTR and E298A polymorphisms of the eNOS gene were evaluated in the isolated DNA blood samples obtained from the SCF patient group (n = 30) and healthy group consisted of age- and sex-matched controls (n = 61).ResultsPlasma NOx level was significantly lower in patients with SCF than in controls. In addition, patients with SCF have significantly lower nitric oxide levels than control subjects within each genotype variants. The allele and genotyped frequencies of the eNOS intron 4 VNTR and E298A polymorphisms were similar between patients with SCF and the controls. Plasma NOx concentrations with respect to the relevant genotypes were found insignificant.Discussion and conclusionPlasma NOx is lower in patients with SCF than in healthy subjects. Our findings may suggest the lack of association between intron 4 VNTR and E298A polymorphisms of the eNOS gene and SCF.