Oxide Synthase Gene Polymorphisms Research Articles

Асоціація окремих показників ендотеліальної функції з T894G поліморфізмом гена ендотеліальної синтази монооксиду азоту у хворих на гіпотиреоз і супутній хронічний холецистит

Досліджено асоціацію T894G поліморфізму гена eNOS з окремими показниками ендотеліальної функції у хворих на гіпотиреоз і супутній хронічний некалькульозний холецистит. У пацієнтів із Т-алеллю відзначено вірогідне зростання на 33,1 % (P = 0,01) кількості десквамованих ендотеліоцитів у крові порівняно з такою в обстежених носіїв GG-генотипу. Також встановлено на 10,4 % (P = 0,04) вищу концентрацію загальних стабільних метаболітів монооксиду азоту та на 10,8 % (P = 0,02) більший рівень нітрат-аніонів у крові щодо групи порівняння. У хворих на гіпотиреоз із супутнім хронічним холециститом вміст судинного ендотеліального фактора росту в носіїв T-алелі на 27,7 % (P = 0,03) переважав такий у пацієнтів із GG-генотипом.

Association between Endothelial nitric oxide synthase and Hepatic lipase gene polymorphisms with the risk of coronary artery disease in Southern Iran population – A case control study

Coronary artery disease is a multifactorial genetic disease caused by the interaction between genetic and environmental factors. Angiography is the gold standard method for the diagnosis and determining the stage of cardiac disorder. The rs1800588 at the Hepatic Lipase gene and rs1799983 at the endothelial nitric oxide synthase (eNOS) gene are two candidate SNP that result in increased risk of this disease. The aim of this study was to find out the associations of the two mentioned polymorphisms with angiographically proven coronary artery patients in a southern Iranian population. In this study, this two polymorphisms in 287 patients and 229 matched controls were confirmed by angiography and analyzed. Genotype analysis was carried out by PCR and RFLP. Data showed that a significant difference for the eNOS gene polymorphism (p = 0.004) and a non-significant difference for the Hepatic lipase polymorphism (p = 0.261) and increasing severity of angiographic evidences of coronary artery disease were observed. Conclusively the significant association of the G894T with the narrowing of two or three coronary vessels of this patients in an Iranian population have been detected.

Association of endothelial nitric oxide synthase gene (G894T) polymorphism and hypertension in diabetic Bataknese patients.

Aim To assess endothelial nitric oxide synthase (eNOS) gene (G894T) polymorphism and nitric oxide (NO) level in hypertensive diabetic Bataknese patients. Methods A hospital-based, case control study (hypertensive and normotensive diabetic patient) was conducted. Genotyping of eNOS gene (G894T) was done using polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP). Nitric oxide was quantified by sandwich enzyme-linked immunosorbent assay (Sandwich ELISA). Results GT polymorphism and T allele were higher in the hypertensive diabetic patients, 37.5% (p=0.6) and 54% (p=0.39), respectively. Nitric oxide level tended to be lower in the hypertensive diabetic patients (88.87µmol/L) comparing to the normotensive (95.42 µmol/L (p=0.54), as well as GT and TT polymorphism type (p=0.75). Conclusion eNOS gene (G894T) polymorphism is not associated with NO level and hypertension in the diabetic Bataknese patients.

English

English

Association of endothelial nitric oxide synthase (eNOS) gene polymorphisms and physical fitness levels with plasma nitrite concentrations and arterial blood pressure values in older adults.

Endothelial nitric oxide synthase (eNOS) gene polymorphisms are associated with reduced eNOS activity and nitric oxide (NO) production leading to an increase in blood pressure (BP). Regular exercise is the main strategy to minimize the deleterious effects of polymorphisms. However, due to the differences that physical exercise can be performed, some controversial results are found. Therefore it seems reasonable to evaluate the training status (TS). Thus, this study aimed to investigate the association of eNOS gene haplotypes and different levels of TS on nitrite concentrations (NO2-) and BP values in older adult. 424 elderly performed the following assessments: General Functional Fitness Index (GFFI) to estimate TS, systolic and diastolic blood pressure (SBP and DBP), blood collection for analysis of NO2- and g.-786T>C, intron 4b/a (VNTR) and 894G>T polymorphisms. Multivariate logistic regression showed that NO2- was influenced by GFFI and 4b/4a Intron 4. Regarding BP, GFFI influenced SBP and DBP, and just intron 4 was associated with variations in DBP. It can be observed that GFFI affected the NO2-, SBP and DBP independently of haplotypes. Therefore, maintenance of good level of TS can overcome the negative influence of genetics factors (intron 4) by increasing NO2- concentration and decreasing BP values.

THE ROLE OF VARIABILITY OF CANDIDATE GENES eNOS, MnSOD2, ADRB1 IN THE DEVELOPMENT OF CARDIOVASCULAR PATHOLOGY IN NEWBORN

The study of gene polymorphism has been carried out to inform health care practitioners on genetic studies that can be used in clinical practice, and the genes under investigations aim at finding early manifestations of cardiovascular disorders. The possibility of determining the ways of correction of the detected cardiovascular pathology necessitates the prospect of further research starting from the neonatal period. To study the frequency of occurrence of genotypes of endothelial nitric oxide (eNOS) gene candidates polymorphism, mitochondrial superoxide dismutase (MnSOD2) 1 mutation and β1-adrenoreceptor (ADRB1) gene polymorphism in neonatal infants from perinatal risk groups the study involved examination of 186 newborns: 102 healthy full-term newborns, 25 newborns after asphyxia, 46 premature newborns and 13 newborns with intrauterine growth retardation. The study showed that the frequency of distribution of endothelial nitric oxide synthase (eNOS) C786T genotypes, mitochondrial superoxide dismutase (MnSOD2) T49C and β1-adrenergic receptor (ADRB1) Ser49Gly in newborns from perinatal risk groups in the neonatal period did not differ from healthy neonates.The CT genotype (p<0.05) of the endothelial nitric oxide synthase (eNOS) gene polymorphism C786T can be considered one of the predictors of cardiovascular development in newborns, which requires further clinical and instrumental comparison. Information on the prevalence of polymorphisms of genes associated with the development of cardiovascular events should be considered when developing a set of individual preventive measures.

Association between endothelial nitric oxide synthase gene (T786C) Polymorphism and hypertensive disorder of pregnancy: a meta-analysis

目的 系统评价内皮型一氧化氮合酶（endothelial nitric oxide synthases，eNOS）基因T786C多态性与妊娠期高血压疾病（hypertensive disorders of pregnancy，HDP）易感性的相关性。 方法 检索Pubmed、Cochrane Library、Embase、中国期刊全文数据库、万方数据库和中国生物医学文献数据库关于eNOS基因T786C多态性与HDP的相关研究。检索时限为数据库建库至2015年12月16日。由2名研究者各自独立评价纳入文献的质量，提取相关资料后，利用Stata 12.0软件进行meta分析。 结果 共纳入14篇文献，其中13篇英文文献，1篇中文文献；2 371例HDP患者和2 912例对照者。Meta分析结果显示：（1）总体人群：eNOS基因T786C多态性与HDP易感性无相关性，在显性模型、隐性模型、纯合子模型和杂合子模型中OR值（95%CI）分别为1.06（0.91~1.24）、1.30（0.98~1.72）、1.32（0.95~1.83）和1.03（0.91~1.17），P值均>0.05。（2）不同种族人群：亚洲和美洲人群eNOS基因T786C多态性与HDP易感性无相关性（P值均>0.05），欧洲人群的eNOS基因T786C多态性与HDP易感性存在相关性，在显性模型、隐性模型及纯合子模型中OR值（95%CI）分别为1.37（1.09~1.71）、1.55（1.16~2.05）和1.76（1.28~2.41），P值均<0.05。 结论 eNOS基因T786C多态性可能与欧洲人群HDP易感性有关，但需要高质量、大样本的研究进一步验证。

Endothelial Nitric Oxyde Synthase Gene Polymorphisms in a Tunisian Deep Vein Thrombosis Group

Deep vein thrombosis (DVT) is a multi-factorial disease involving both genetic and acquired risk factors. The objective of this study was to determine the frequencies of endothelial nitric oxide synthase (eNOS) gene polymorphisms G894T (rs1799983) and T-786C (rs2070744) to assess the role of these polymorphisms as a potential risk factor in the development of DVT. Methods: In this case-control study, we included 32 patients with deep vein thrombosis (DVT) and 31 healthy control subjects. Clinical characteristics were collected. Lipids plasma concentrations were determined by the colorimetric method. Genotyping for the polymorphisms was performed by restriction fragment length polymorphism (PCR-RFLP) method. Results: We had found that the eNos G894T genotype G/T was significantly increasing the risk of DTV (P = 0.042, OR = 3.9; 95% CI = 1.09 to 13.92). But no association of the eNOS T-786C variant and DVT was found. For the eNOs T-786C polymorphism, the frequency of the T/T genotype was 87.5% in patients (with an allelic frequency of T Allele equal to 91%). No significant difference was noted between the two groups (P > 0.05). Conclusion: The eNOs G894T polymorphism seems to be in association with DVT and may be considered as a risk factor, but this is not the case for the T-786C polymorphism.

Nitric oxide synthase and endothelin-1 gene polymorphism in lower limb chronic venous insufficiency

Objective of this study was to evaluate the prevalence of endothelin-1 (EDN1 Lys198Asn) and nitric oxide synthase (NOS3 C786T) gene polymorphism in patients with lower limb chronic venous insufficiency; a possible correlation between gene polymorphism and degree of chronic venous insufficiency was also considered. The study included 240 patients with lower limb chronic venous insufficiency. The main group included 160 patients with venous ulcers; control group included 80 patients without ulceration. Peripheral venous blood samples were taken for DNA evaluation. EDN1 Lys198Asn mutation for endothelin-1 and NOS3 C786T mutation for nitric oxide synthase were studied. Detection of polymorphism in genes, which determine the development of endothelial dysfunction in lower limb chronic venous insufficiency, represents a useful tool to predict the severity of the disease and its outcomes.

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.

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

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

Effect of eNOS polymorphisms on salbutamol evoked endothelium dependent vasodilation in South Indian healthy subjects

Background:The model of pulse plethysmograph using inhalational salbutamol 400 mcg is studied well to assess endothelium dependent vasodilation. Endothelial nitric oxide synthase (eNOS) gene polymorphism may influence the response to salbutamol in healthy subjects.Aim:To find the effect of polymorphisms 894G>T and -786T>C of eNOS gene on endothelium dependent vasodilation in healthy subjects.Materials and Methods:One hundred and two south Indian healthy subjects of either sex, aged between 18 to 35 years were recruited for the study. The digital volume pulse (DVP)was measured by pulse plethysmograph before and after salbutamol 400mcg inhalation. Three predose and five postdose recordings of DVP were measured. The average change in the DVP parameters namely reflection index (RI) and stiffness index (SI) were determined. The eNOS894G>T and -786T>C gene polymorphism were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism. The percentage changes in RI and SI from predose baseline recordings were calculated and compared between the genotype groups.Results:The genotype and allele frequency of study subjects were in Hardy-Weinberg equilibrium. The changes in DVP parameters were not significantly different between the genotype groups.Conclusion:eNOS polymorphism do not affect salbutamol evoked endothelium dependent vasodilation in the model of pulse plethysmograph in healthy subjects.

88-P

Aim It is known that NO has a relevant role in inflammation, vascular and muscular tonus in asthma. Endothelial nitric oxide synthase (eNOS) modulates the amount of NO that could be related with eNOS polymorphisms. The purpose of this study is to analyze the association between endothelial nitric oxide synthase (eNOS) gene polymorphism eNOS intron 4 Ins/del (eNOS 4 a/b-27 bp-base pairs) with asthma severity. Methods Asthmatic patients: n = 31; were compared with a control group of n = 174 healthy blood donors. The Ins/del polymorphism (eNos 4 a/b) was determined by PCRPolymerase chain reaction. Control of asthma assessed by validated instrument (ACQ7 and PAQLQ). Statistical analysis was performed with PASW version 18 and Primer of biostatistics, establishing a significance level of p Results The mean age of the 31 asthmatics was 40 ± 19.5 years; minimum 12 and maximum 86: 15 females and 16 males; all caucasians; 28 atopics and 3 nonatopics; 20 with controlled and 11 with uncontrolled asthma. In asthmatics the frequencies of the Ins/del polymorphism (eNos 4 b) is 87% and of the Ins/del polymorphism (eNos 4 a) is 13%; in controls: 80% and 20% respectively. There is no statistical difference between these groups (p > 0.05).Genotypes in the asthmatics-bb: 77.4%; aa: 3.2%; ab: 19.4%; in control group-bb: 67.82%; aa: 8.6%; ab: 23.56%. There is no statistical difference between these groups(p > 0.05).In asthmatics, there is no statistical difference (p > 0.05): atopics and non atopics; controlled and uncontrolled asthma; males and females; and in the different age-groups. Conclusions The role of eNOS gene intron 4 a/b Ins/del polymorphism in asthmatics is a controversial risk factor to the severity of asthma, but we think that we need a larger sample to infer about its role in inflammation and in vascular and muscular tonus homeostasis in asthmatic disease.

799: Endothelial nitric oxide synthase (eNOS) gene polymorphisms and risk for preeclampsia: a metaanalysis

799: Endothelial nitric oxide synthase (eNOS) gene polymorphisms and risk for preeclampsia: a metaanalysis

Effect of exercise training on the cardiovascular and biochemical parameters in women with eNOS gene polymorphism

Context: Presence of endothelial nitric oxide synthase (eNOS) gene polymorphism has been associated with cardiovascular disease (CVD) whereas exercise training (EX) promotes beneficial effects on CVD which is related to increased nitric oxide levels (NO).Objective: To evaluate if women with eNOS gene polymorphism at position−G894T would be less responsive to EX than those who did not carry T allele.Methods: Women were trained 3 days/week, 40 minutes session during 6 months. Cardio-biochemical parameters and genetic analysis were performed in a double-blind fashion.Results: Plasma NOx− levels were similar in both groups at baseline (GG genotype: 18.44 ± 3.28 μM) and (GT + TT genotype: 17.19 ± 2.43 μM) and after EX (GG: 29.20 ± 4.33 and GT+TT: 27.38 ± 3.12 μM). A decrease in blood pressure was also observed in both groups.Discussion and conclusion: The presence of eNOS polymorphism does not affect the beneficial effects of EX in women.

Plasma Total Nitric Oxide and Endothelial Constitutive Nitric Oxide Synthase (ecNOS) Gene Polymorphism: A Study in a South Indian Population

In an analysis of the possible association of endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphism and plasma nitric oxide levels in patients with acute coronary syndrome, we investigated 106 patients with the syndrome and 100 healthy controls. Genotype was determined using the polymerase chain reaction; plasma nitric oxide levels were found using ELISA. The genotype frequencies for the a/b polymorphism in the control group were 77% for bb, 19% for ab, and 4% for aa. In the patients, genotype frequencies were 55% bb, 34% ab, and 11% aa. The allele frequencies were 28% a and 72% b among the patients and 13% a and 87% b among control subjects. Our findings showed a significant association of the ecNOS gene polymorphism with acute coronary syndrome in the South Indian population.

Lack of association between endothelial constitutive nitric oxide synthase (ecNOS 4 b/a) gene polymorphism and rheumatic heart disease

Our aim in this work was to explore any possible association between ecNOS 4 b/a polymorphism and rheumatic heart disease (RHD). In this study, leukocyte DNA was extracted from 139 patients with RHD and 79 healthy control children. After amplification by PCR, the products were separated by electrophoresis in 6% polyacrylamide gel and visualized after ethidium bromide staining with UV light. PCR resulted in a 420-bp fragment (ecNOS4b) when five 27-bp repeats were present in intron 4 of the ecNOS gene, a 393-bp product (ecNOS4a) when only four repeats were present, and 420-bp and 393-bp fragments in heterozygous individuals (ecNOS4b/a). ecNOS4b/a genotyping in the control group gave the following results: b/b genotype (77.2%), b/a genotype (21.5%) and a/a genotype (1.3%). The frequencies in RHD group were as follows: b/b genotype (67.6%), b/a genotype (31.7%), and a/a genotype (0.7%). The b allele/a allele ratio was (88%/12%) in the control group and (83.5%/16.5%) in the RHD group. We found no statistical difference in genotype or allele frequency between these groups. The present study is the first to study the association between ecNOS 4b/a gene polymorphism and RHD, and to find a lack of any association between them. Further investigations of this gene polymorphism alone and in combination with other genes should be encouraged.

Lack of association between endothelial constitutive nitric oxide synthase (ecNOS 4 b/a) gene polymorphism and rheumatic heart disease

Our aim in this work was to explore any possible association between ecNOS 4 b/a polymorphism and rheumatic heart disease (RHD). In this study, leukocyte DNA was extracted from 139 patients with RHD and 79 healthy control children. After amplification by PCR, the products were separated by electrophoresis in 6% polyacrylamide gel and visualized after ethidium bromide staining with UV light. PCR resulted in a 420-bp fragment (ecNOS4b) when five 27-bp repeats were present in intron 4 of the ecNOS gene, a 393-bp product (ecNOS4a)when only four repeats were present, and 420-bp and 393-bp fragments in heterozygous individuals (ecNOS4b/a). ecNOS4b/a genotyping in the control group gave the following results: b/b genotype (77.2%), b/a genotype(21.5%) and a/a genotype (1.3%). The frequencies in RHD group were as follows: b/b genotype (67.6%), b/a genotype (31.7%), and a/a genotype (0.7%). The b allele/a allele ratio was (88%/12%) in the control group and (83.5%/16.5%) in the RHD group. We found no statistical difference in genotype or allele frequency between these groups. The present study is the first to study the association between ecNOS 4b/a gene polymorphism and RHD, and to find a lack of any association between them. Further investigations of this gene polymorphism alone and in combination with other genes should be encouraged.

Protective role of 27bp repeat polymorphism in intron 4 of eNOS gene in lacunar infarction

Association of the three potential endothelial nitric oxide synthase gene (eNOS) polymorphisms (T-786C in promoter region, G894T in exon 7 and tandem 27-bp repeats in intron 4) with an increased risk of lacunar infarction (LI) were investigated. Genotypes of 70 patients and 81 healthy controls were determined through PCR with or without RFLP. Flow-mediated dilatation (FMD) was performed to assess endothelial-dependent vasodilatation, whereas the endothelial-independent vasodilatation was assessed with nitroglycerin (NTG). Genotype distribution was significantly different between LI patients and controls for intron 4aa (alleles for four repeats), genotype frequency being 1.4% and 16.0%, respectively (odds ratio for additive effect, 0.47; 95% CI, 0.28–0.81; p=0.006). Haplotypes with the intron 4aa polymorphism were significantly higher in controls when compared with the LI group (p=0.001). Diminished FMD but normal NTG response confirmed that patients with LI have generalized endothelial dysfunction. Intron 4aa genotype of eNOS gene seems to be protective for isolated LI and the effect was potentiated by the absence of 786C polymorphism in any allele of the promoter region.

Endothelial nitric oxide synthase (e-NOS) gene polymorphism (Glu298Asp) and pulmonary hypertension in children with congenital heart diseases

Endothelial nitric oxide synthase (e-NOS) gene polymorphism (Glu298Asp) and pulmonary hypertension in children with congenital heart diseases