eNOS Polymorphisms Research Articles

Association of clinical and genetic factors with left ventricular hypertrophy in hypertension among the indigenous population Mountain Shoria

Objective. To determine the association of clinical and genetic factors with the left ventricular hypertrophy among indigenous patients with hypertension living in Mountain Shoria.Design and methods. A clinical-epidemiological study of Mountain Shoria indigenous populations at isolated regions was undertaken. Continuous method surveyed 547 people, consisted of a sample of the adult population (18 years and older). Studied anthropometric data, lipid spectrum of the blood polymorphisms of genes ADRB1 (Ser49Gly, A/G, rs1801252) ADRA2B (I/D), ACE (I/D), eNOS (4a/4b) and MTHFR (C677T, Ala222Val, rs1801133) and their association with left ventricular hypertrophy.Results. The left ventricular hypertrophy in patients with hypertension was detected in 47.3% of the respondents. The odds ratio found among patients with hypertension duration of 5 years with the respondents hypertrophied myocardium 0.5 times lower (38.2%) than people without this disease of the heart - 61.8%, while among those with hypertension long history of more than 10 years, 4.1 times higher: 73.3% vs 26.7%. In a population of Shor hypercholesterolemia and giperbetaholesterinemiya associated with exaggerated myocardial damage. The percentage of smokers in a cohort of patients with hypertensive cardiac disease was (37.8%) and was higher by 2.0 times than in hypertensive patients without left ventricular hypertrophy (22.0%). With the relative risk of hypertension with myocardial damage in a population Shor associated gene ACE I allele. The odds ratio of hypertension to identify patients with cardiac respondents with heterozygous genotype AG ADRB1 gene was 3.0 times higher compared to the surveyed individuals with homozygous genotypes AA and GG.Conclusion. Among Shor risk of hypertension with left ventricular hypertrophy was influenced by factors: prolonged duration of the disease more than 10 years, smoking, hypercholesterolemia, giperbetaholesterinemiya. Installed Association II genotype of ACE gene and gene genotype AG ADRB1s development of left ventricular hypertrophy in patients with arterial hypertension in the population of Shor.

Genetic contributing factors to substance abuse: an association study between eNOS gene polymorphisms and cannabis addiction in a Turkish population

It is known to be largely related to behavioural changes and neuropsychiatric disorders, and studies demonstrating the influence of eNOS gene variants in the development of depressive, aggressive and suicidal behaviours exist in the literature. Here, we investigate two polymorphisms in the eNOS gene, namely, G894T (Glu298Asp) and intron 4 VNTR, as possible genetic contributing factors to cannabis addiction. DNA samples used in this work were purified from the peripheral blood of 94 unrelated Turkish cannabis-dependent subjects and 100 Turkish control subjects from the southeastern region of Turkey. The eNOS polymorphisms were characterised by the PCR and/or PCR-RFLP (Polymerase Chain Reaction-restriction fragment length polymorphism) method. The De-finetti programme, chi-square, Fisher’s exact test, odds ratio and 95% confidence intervals (CI) were used for statistical analysis. The incidence of aa and TT genotypes and the frequency of the alleles a and T were found to be significantly higher in the cannabis addicts group than in the control subjects (p < 0.05). The results indicate that G894T and intron 4 VNTR eNOS gene polymorphisms are statistically-significant contributing factors to susceptibility to cannabis addiction, while the same polymorphism alleles associated with high NO levels are a protective factor in Turkish subjects. To the best of our knowledge, this is the first study on eNOS gene polymorphisms involving the Turkish population.

Associations between endothelial nitric oxide synthase polymorphisms and risk of diabetic nephropathy: an updated meta-analysis

Background: Genetic polymorphism of endothelial nitric oxide synthase (eNOS) has been implicated in the risk of diabetic nephropathy (DN), but the published findings were inconsistent. We performed a comprehensive meta-analysis to derive a more precise estimation of the association between genetic polymorphisms of eNOS and the risk of DN. Methods: Six online database were researched on the associations between polymorphisms of eNOS (T786C, G894T, 4b/4a) and DN risk. PRISMA statement and Hardy–Weinberg equilibrium assessment were used in this report. Odds ratio and 95% confidence interval were estimated based on the following genetic contrast/models: allelic model, dominant model, recessive model and co-dominant model. The publication bias and sensitivity analysis were also performed to guarantee the statistical power. Results: A total of 49 case–control studies with 11,990/9754/5131 participants for DN/DM/HC group were eligible for meta-analysis (7/25/31 studies for T786C/G984T/4b/a). For the eNOS-T786C, C allele showed a weak association between C allele and DN risk in DN/T2DM group. For eNOS-G894T, there was an association between T allele and DN risk in the global, Asian and African population in DN/T2DM group. For the eNOS-4b/4a, 4a allele was found contributing significantly to increased DN risk in the global population. Conclusion: Our comprehensive meta-analysis suggests that three polymorphisms of eNOS may be the increased risk factors of DN development, especially in Asian population and T2DM group.

Analyses of C-Reactive Protein, Endothelial Nitric Oxide Synthase and Interleukin-6 Gene Polymorphisms in Adolescents with a Family History of Premature Coronary Artery Disease: A Pilot Study.

Family history of premature atherosclerosis imposes a high risk to people. The relationship between atherosclerosis and gene polymorphisms of various biomarkers such as Endothelial Nitric Oxide Synthase (eNOS), C-Reactive Protein (CRP), and Interleukin-6 (IL-6) has shown in previous studies. The major aim of the study was to evaluate the CRP, eNOS, and IL-6 gene polymorphisms in a group of adolescents who have a parental history of early coronary artery disease (CAD). Case-control study. Thirty-six volunteers with a father with obstructive CAD during the first four decades and 46 subjects with a father with normal coronary arteries documented with coronary angiography were included in the study. Polymerase chain reaction-restriction fragment length polymorphism techniques were used to analyze CRP, eNOS, and IL-6 polymorphisms. We did not find any differences between the two groups with regard to age, sex, body mass index, renal functions, systolic and diastolic blood pressures, lipid profile, and fasting glucose, hemoglobin, and high sensitivity CRP. A significant difference was only observed in IL-6-572 G/C genotype distribution and allele frequency between two groups (Pc=0.036 OR=3.48 CI (95%) 1.17-10.32). The present study showed a significant association between the IL-6-572 G/C gene polymorphism (presence of C allele) and adolescents with a parental history of premature CAD.

L05 - eNOS polymorphisms in relation to outcome in advanced HCC patients receiving sorafenib. Final results of ePHAS study

L05 - eNOS polymorphisms in relation to outcome in advanced HCC patients receiving sorafenib. Final results of ePHAS study

Gene polymorphisms determining physical performance in Ukrainian power-oriented events of track and field athletics

Summary Research background and hypothesis. Modern research on the molecular genetics of physical activity shows that increased physical performance is determined by a set of specific genes. However, the systematic genetic studies of high performance athletes for selection and training purposes do not exist to our knowledge and there are no studies for specific sports, which could have made the specialization choices easier . Research aim was to analyse important genetic variations that may underlie differences in the potential to be an elite athlete of power-oriented events of track and field athletics . Research methods. In total, DNA of 73 athletes involved in power-oriented events of track and field athletics and 283 persons not involved in sports (sedentary control) were examined. In this paper, we consider ten candidate-genes and carry out statistical analysis to determine their most favourable polymorphism for power-oriented events of track and field athletics. Using the polymerase chain reaction method І/D (АСЕ), R577X (ACTN3), Т -786 →С (eNOS), Pro/ Ala (PPARG), G/C (PPARA), Pro 582 →Ser (HIF-1α), Ala203Pro (PPARGC1B), C-1306T (MMP2), Ser422Gly (ELN), Tag1A (DRD2) genes polymorphisms were detected in athletes of different abilities. Research results. The significance of differences between group of power-oriented events of track and field athlet ics and the control group on the distribution of allele NO-synthase gene polymorphism and distribution of genotype of metalloproteinase 2 gene polymorphism was found. The frequency of T allele Т -786 →С polymorphism eNOS prevails in the group of athletes by 11.5% (p = 0.02). The frequency of T/T genotype C-1306T (MMP2) is 11.8% (p = 0.003) higher than in the control group. The athletes specializing in different events are characterized by genetic heterogeneity. Favourable alleles for high athletic performance in power-oriented events of athletics were established. Discussion and conclusions. Sports genetics can be used to design better selection and training processes in order to allow athletes to achieve their full potential. Our study provides evidence for the association between gene polymorphisms and elite power athlete status. However, athletes belonging to the same group of sports differ in the distribution of genotypes and allele of gene that associate with elite performance. Only after detection of favourable genotype combination for the particular sport potential of genetic testing in sport will be increased.

The association between no-synthases gene polymorphisms and post-traumatic knee ostearthritis development among Rostov region residents

Background. Knee osteoarthritis (OA) is a common chronic degenerative disease. The risk factors for the development of knee OA are joint trauma and genetic predisposition. The aim of the present work was to study the associations between gene polymorphisms -84G A nNOS and -786T C eNOS and the risk of post-traumatic knee osteoarthritis (PTOA) development among Rostov region residents and to define the interactions between these polymorphisms and nitrite level in the plasma and synovial fluid (SF) and chondrocyte apoptosis in patients with PTOA. Materials and Methods. Case-control study involved 117 post-traumatic knee OA patients and 94 healthy controls. The nNOS and eNOS polymorphisms were determined by polymerase chain reaction. The nitrite concentrations in the plasma and synovial fluid were defined using Griess reaction. Chondrocyte apoptosis in cartilage sections was assessed morphologically by electron microscopy. Results. The G-84A nNOS genotype showed statistical differences between groups. The A allele is associated with PTOA development (OR 2,02, CI 1,08-3,76, p = 0,02). The eNOS genotype did not show statistical difference between groups. The NOx- concentration was higher both in plasma (p = 0,022) and synovial fluid (p = 0,014) of PTOA patients compared with plasma of healthy subjects. Multiple regression analyses demonstrated that the nitrite level in the SF is linked with -786T C NOS3 genotype; the -786С allele leaded to the decreasing in NOx- concentration. The electron microscopy confirmed the presence of early and late apoptotic chondrocytes in PTOA cartilage tissue. Conclusion. The G-84A nNOS polymorphism may be associated with PTOA development and chondrocyte apoptosis intensification. The -786С allele of -786T C NOS3 is associated with reduced NOx- concentration in the synovial fluid.

AB197. Endothelial nitric oxide synthase polymorphism and erectile dysfunction risk: evidence based on a meta-analysis

ObjectiveThe association between eNOS polymorphism and erectile dysfunction risk remains conflicting. We conducted a meta-analysis to examine the eNOS T894G, 4VNTR, C-786T polymorphism in relation to the susceptibility of erectile dysfunction.MethodsStudies concerning this association were searched and related information was extracted from the included studies. The STATA 12.0 software was used to perform a meta-analysis.ResultsSignificant association was observed between eNOST894G polymorphism and erectile dysfunction risk for all genetic models (T vs. G: OR =1.73; 95% CI, 1.52-1.97; P=0.000; TT vs. GG: OR =1.99; 95% CI, 1.40-2.84; P=0.000; TG vs. GG: OR =1.67; 95% CI, 1.42-1.98; P=0.000; TT+TG vs. GG: OR =1.89; 95% CI, 1.61-2.22; P=0.000; TT vs. TG+GG: OR =2.33; 95% CI, 1.69-3.22; P=0.000; TG vs. TT+GG: OR =1.47; 95% CI, 1.25-1.73; P=0.000). Subgroup analysis by population produced significant results in Asian population as well. The meta-analyses of 4VNTR and C-786T polymorphism yielded inconsistent results.ConclusionsIn conclusion, the results of the meta-analysis indicated that the T allele of eNOS gene T894G polymorphism is a risk factor for erectile dysfunction in Asians. However, the results should be interpreted with caution and further studies are required.

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

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

Clinical Relevance of MTHFR, eNOS, ACE, and ApoE Gene Polymorphisms and Serum Vitamin Profile among Malay Patients with Ischemic Stroke

The purpose of this study was threefold. First, it was to determine the relationship between serum vitamin profiles and ischemic stroke. The second purpose was to investigate the association of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and apolipoprotein-E (ApoE) gene polymorphisms with ischemic stroke and further correlate with serum vitamin profiles among ischemic stroke patients. The third purpose of the study was to highlight the interaction of MTHFR and eNOS haplotypes with serum vitamin profiles and ischemic stroke risks. Polymorphisms of these genes were analyzed in age-, sex-, and ethnicity-matched case-controls (n=594); serum vitamin profiles were determined using immunoassays. The MTHFR 677C>T, 1298A>C, eNOS intron 4a/b, and ApoE polymorphisms were significantly associated with the increased risk of ischemic stroke. Elevated serum homocysteine and vitamin B12 levels were associated with MTHFR 677C>T and eNOS intron 4a/b polymorphisms. The ApoE and eNOS -786T>C polymorphisms were associated with increased serum vitamin B12 levels. However, none of the polymorphisms influenced serum folate levels except for the MTHFR 1298A>C. Different patterns of MTHFR and eNOS haplotypes tend to affect serum vitamin profiles to different degrees, which contribute to either different susceptibility risk or protective effect on ischemic stroke. Overall, increased levels of serum homocysteine and vitamin B12 levels were associated with higher risk of ischemic stroke in the investigated population. The present study suggests that the genotypes and haplotypes of MTHFR 677C>T and eNOS intron 4a/b polymorphisms are potential serum biomarkers in the pathophysiological processes of ischemic stroke, by modulating homocysteine and vitamin B12 levels.

Genetic Contributions to the Development of Complications in Preterm Newborns.

AimWe aimed to identify specific polymorphisms of genes encoding for vascular endothelial growth factor A (VEGFA), endothelial nitric oxide synthase (eNOS), renin-angiotensin system (angiotensinogen gene [AGT], angiotensinogen type 1 receptor [AGTR1], angiotensin-converting enzyme [ACE]), and heme oxygenase-1 (HMOX-1) in a cohort of preterm infants and correlate their presence with the development of respiratory distress syndrome (RDS) requiring mechanical ventilation (MV), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP).Study DesignWe carried out a retrospective study to evaluate the allele frequency and genotype distribution of polymorphisms of VEGFA, eNOS, AGT, AGTR1, ACE, and HMOX-1 in a population of preterm neonates (n=342) with a gestational age ≤28 weeks according to the presence or absence of RDS requiring MV, BPD, IVH, or ROP. Moreover, we evaluated through the haplotype reconstruction analysis whether combinations of the selected polymorphisms are related to the occurrence of RDS, BPD, IVH and ROP.ResultsIn our population 157 infants developed RDS requiring MV, 71 BPD, 70 IVH, and 43 ROP. We found that TC+CC rs2070744 eNOS (41.7 vs. 25.4%, p=0.01) and GT+TT rs1799983 eNOS (51.8 vs. 35.2%, p=0.01) polymorphisms are independent risk factors for BPD. Haplotype reconstruction showed that haplotypes in VEGF and eNOS are significantly associated with different effects on RDS, BPD, IVH, and ROP in our population.ConclusionsWe found that TC+CC rs2070744 eNOS and GT+TT rs1799983 eNOS polymorphisms are independent predictors of an increased risk of developing BPD. Haplotypes of VEGFA and eNOS may be independent protective or risk markers for prematurity complications.

Association of IL-8 and eNOS polymorphisms with clinical outcomes in bevacizumab-treated breast cancer patients: an exploratory analysis.

The role of bevacizumab in metastatic breast cancer is controversial. Identification of predictive biomarkers could help to select patients who really benefit from it. We evaluated the association of angiogenesis-related gene polymorphisms with the treatment outcome of bevacizumab in metastatic breast cancer patients. eNOS-786T/C and -894G/T, IL-8-251T/A genomic polymorphisms were assessed in 31 metastatic breast cancer patients treated with bevacizumab plus chemotherapy in the first-line setting. Testing for association between each polymorphism and treatment outcome was performed. Patients with IL-8 251 AA genotype showed a significantly lower progression-free survival in each combination comparison: "TT" vs "AA" (13 vs 8 months; p = 0.008); TT vs TA vs AA (13 vs 11 vs 8 months; p = 0.02); TT vs TA +AA (13 vs 11 months; p = 0.01); TT + TA vs AA (12 vs 8 months; p = 0.01) and a lower overall survival when compared with TT +TA genotype (26 vs 51 months, p = 0.04). Patients carrying eNOS 894 TT genotype showed a statistically significant lower progression-free survival than patients with GG genotype (11.5 vs 26.5 months; p = 0.04) with no differences in the overall survival. No association with response rate was found with any of the polymorphisms analyzed. These findings suggest that IL-8 251T/A and eNOS-894 G/T polymorphisms might have a role in predicting treatment outcome of bevacizumab in metastatic breast cancer. Our results are hypothesis generating and need to be confirmed in larger clinical trials.

ENOS Genetic Polymorphisms and Cancer Risk: A Meta-Analysis and a Case-Control Study of Breast Cancer.

The association between endothelial nitric oxide synthase (eNOS) polymorphisms (intron 4a/b, -786T>C and 894G>T) and cancer risk remains elusive. In addition, no studies focused on their associations with the risk of breast cancer in Chinese Han population. Thus, a meta-analysis was conducted to determine the relationship between eNOS polymorphisms and cancer risk, and then a case–control study in Chinese Han population was performed to assess their associations with breast cancer susceptibility.Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The pooled analysis indicated that eNOS intron 4a/b and -786T>C polymorphisms were significantly associated with an increased risk of overall cancer. In subgroup analyses based on cancer type, the significant association was found between eNOS intron 4a/b polymorphism and prostate cancer risk, eNOS -786T>C polymorphism and risk of prostate, bladder and breast cancers, and eNOS 894G>T polymorphism and breast cancer risk. In subgroup analyses based on ethnicity, eNOS intron 4a/b and -786T>C polymorphisms were associated with an increased risk of cancer in Caucasians. In consistent with our meta-analysis results, a case–control study in Chinese Han population showed significant associations of eNOS -786T>C and 894G>T polymorphisms with the increased risk of breast cancer. In addition, stratified analyses based on pathological type showed that eNOS 894G>T polymorphism was only associated with the risk of infiltrative ductal carcinoma. Stratified analyses by tumor stage showed that eNOS -786T>C polymorphism was only associated with the risk of tumor stage III and IV.In conclusion, our meta-analysis and case–control study suggest that eNOS -786T>C and 894G>T polymorphisms are associated with the increased risk of breast cancer.

Achalasia Is Associated With eNOS4a4a, iNOS22GA, and nNOS29TT Genotypes: A Case-control Study.

Background/AimsAchalasia is known to result from degeneration of inhibitory neurons, which are mostly nitrinergic. Characteristic features of achalasia include incomplete lower esophageal sphincter (LES) relaxation and esophageal aperistalsis. Nitric oxide (NO), produced by NO synthase (NOS), plays an important role in peristalsis and LES relaxation. Therefore, we evaluated genetic polymorphisms of NOS gene isoforms (endothelial NOS [eNOS], inducible NOS [iNOS], and neuronal NOS [nNOS]) in patients with achalasia and healthy subjects (HS).MethodsConsecutive patients with achalasia (diagnosed using esophageal manometry) and HS were genotyped for 27-base pair (bp) eNOS variable number of tandem repeats (VNTR), iNOS22G/A (rs1060826), nNOS C/T (rs2682826) polymorphisms by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively.ResultsAmong 183 patients (118 [64.5%] male, age 39.5 ± 13.0 years) with achalasia and 366 HS (254 [69.4%] male, age 40.8 ± 11.0 years), eNOS4a4a genotype of 27-bp VNTR was more common among achalasia than HS (20 [10.9%] vs 13 [3.6%]; P < 0.001; OR, 3.72; 95% CI, 1.8–7.7). Patients with achalasia had iNOS22GA genotypes more often than HS (95 [51.9%] vs 93 [25.4%]; P < 0.001; OR, 3.0; 95% CI, 2.1–4.4). Frequency of genotypes GA + AA was higher in patients than HS (97 [53%] vs 107 [29.2%]; P < 0.001; OR, 2.7; 95% CI, 1.8–3.9). Also, nNOS29TT variant genotype in rs2682826 was more common among patients compared to HS (14 [7.7%] vs 6 [1.6%]; P < 0.001; OR, 5.91; 95% CI, 2.2–15.8).ConclusionsAchalasia is associated with eNOS4a4a, iNOS22GA, and nNOS29TT genotypes. This may suggest that polymorphisms of eNOS, iNOS, and nNOS genes are risk factors for achalasia.

Associations of Angiotensin-Converting Enzyme Insertion/Deletion, Angiotensin II Receptor A1166C, and Endothelial Nitric Oxide Synthase 4b/a Gene Polymorphisms With Pregnancy Hypertensive Disorders: A Meta-Analysis.

There have been numerous studies concerning the associations of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D), angiotensin II receptor 1 (AT1R) gene A1166C, and endothelial nitric oxide synthase (eNOS) gene 4b/a polymorphisms with risk of pregnancy hypertensive disorders (PHDs). However, the results are inconsistent. A total of 83 eligible studies (10,354/18,446 cases/controls) were included in this meta-analysis. Pooled odds ratios with corresponding 95% confidence intervals were used to calculate these associations. The effects of ethnicity and types of PHDs were also considered. Results showed significant associations between the ACE gene polymorphism and PHDs in all of the populations except that in Africa. The associations also existed in AT1R, eNOS gene polymorphism and PHDs in part of the gene models in the overall population. These results indicated the ACE gene polymorphism was associated with an increased risk of PHDs, whereas the eNOS and AT1R gene polymorphism only have increased susceptibility to PHDs in part of the gene models.

Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment.

BackgroundCerebral infarction due to thrombosis leads to the most common type of stroke and a likely cause of age-related cognitive decline and dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays a crucial role in maintaining vascular function and exerting an antithrombotic action. Reduced eNOS expression and eNOS polymorphisms have been associated with stroke and Alzheimer’s disease (AD), the most common type of dementia associated with neurovascular dysfunction. However, direct proof of such association is lacking. Since there are no reports of complete eNOS deficiency in humans, we used heterozygous eNOS+/- mice to mimic partial deficiency of eNOS, and determine its impact on cerebrovascular pathology and perfusion of cerebral vessels.ResultsCombining cerebral angiography with immunohistochemistry, we found thrombotic cerebral infarctions in eNOS+/- mice as early as 3–6 months of age but not in eNOS+/+ mice at any age. Remarkably, vascular occlusions in eNOS+/- mice were found almost exclusively in three areas: temporoparietal and retrosplenial granular cortexes, and hippocampus this distribution precisely matching the hypoperfused areas identified in preclinical AD patients. Moreover, progressive cerebral amyloid angiopaphy (CAA), blood brain barrier (BBB) breakdown, and cognitive impairment were also detected in aged eNOS+/- mice.ConclusionsThese data provide for the first time the evidence that partial eNOS deficiency results in spontaneous thrombotic cerebral infarctions that increase with age, leading to progressive CAA and cognitive impairments. We thus conclude that eNOS+/- mouse may represent an ideal model of ischemic stroke to address early and progressive damage in spontaneously-evolving chronic cerebral ischemia and thus, study vascular mechanisms contributing to vascular dementia and AD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-015-0020-0) contains supplementary material, which is available to authorized users.

The Prevalence of Enos and Agtr2 Gene Polymorphism In Patient With Coronary Artery Desease

The Prevalence of Enos and Agtr2 Gene Polymorphism In Patient With Coronary Artery Desease

Ser49Gly polymorphic markers associations of ADRB1 gene and 4a/4b eNOS gene with hypertension and ischemic heart disease among the population of mountain shoria natives

The purpose: to investigate the frequencies of genes ADRB1 and eNOS genotypes and alleles among the population of Mountain Shoria natives (Shors) and their associations with hypertension and ischemic heart disease.Material and methods. Clinical and epidemiological study of the indigenous population of remote Mountain Shoria areas was conducted. 221 people were observed by the continuous method; the sampling included the adult population (18 years and older). Mean age for observed people was 51.07±1.46 years for men, 52.93±0.96 years for women ( p =0.286). Blood pressure measurement was performed by the method of the WHO/ISH (1999). Epidemiological criteria for ischemic heart disease and left ventricular hypertrophy were used on the basis of ECG coding changes by the Minnesota code. Anthropometric data, blood lipid profile, C-reactive protein, 4a/4b polymorphism of eNOS gene, A/G polymorphism of ADRB1 gene were studied.Results. The frequencies of A/G polymorphism genotypes ADRB1 gene in a population of Shors were in Hardy-Weinberg equilibrium (AA - 47.0%, AG - 41.4%, GG - 11.6%). Genotypes of gene eNOS were as follows: 4b/4b - 80.8%, 4a/4b - 18.7%, 4a/4a - 0.5%. The relative risk of hypertension developing at homozygous for the allele A compared with homozygous for the allele G and heterozygous is higher for 1.6 times (95% CI 1.18-2.09, p =0.003). Accordingly, the relative risk of disease for the carriers of the G allele less than for the carriers of allele A and heterozygotes [RR 95% CI 0.35 (0.12-0.99), p =0.035]. The level of systolic blood pressure is higher at homozygotes AA (137.8±2.5 mm Hg) in comparison with homozygous GG (127.4±4.0 mm Hg). AA genotype carriers had an increased risk of ischemic heart disease in comparison with genotypes AG and GG. The analysis of associations for 4a/4b polymorphism eNOS gene with phenotypic traits among the indigenous ethnic group didn’t reveal any statistically significant patterns.Conclusion. The connection between A/G polymorphism of ADRB1 gene and risk factors of ischemic heart disease (with a help of C-reactive protein, atherogenic index).A allele of ADRB1 gene among the Shor population is associated with the risk of hypertension and ischemic heart disease.

Endothelial nitric oxide synthase polymorphisms and erectile dysfunction: a meta-analysis.

Erectile dysfunction (ED) is a frequent disorder in men and has a serious impact on the quality of the patient's life. Recent studies have examined the relationship between endothelial nitric oxide synthase (eNOS) polymorphisms and ED. However, the results remain inconclusive. The present study aimed to offer an actual view of estimating the correlation between eNOS polymorphisms and ED. We performed a meta-analysis to estimate the association between eNOS polymorphisms and ED risk. Databases employed for data mining until December 1, 2014 included PubMed, Web of Science, and the Chinese National Knowledge Infrastructure. Two study investigators independently conducted a literature search and data extraction. Odds ratios (ORs) with 95% confidence intervals for the risk were calculated by using a random effects model or fixed effects model. A total of 20 studies in 13 publications increased ED risk in allele contrast, dominant, heterozygote, and homozygote models (allele contrast: OR = 1.514, 95% confidence interval were included in the meta-analysis. In the overall comparison, the eNOS G984T polymorphism was associated with an [CI]: 1.019-2.248). For 4 VNTR polymorphisms, the overall analysis showed a significant association between homozygote comparison and recessive genetic model (homozygote comparison: OR = 1.917, CI: 1.073-3.424). The eNOS T786C polymorphism increased ED risk in allele contrast, homozygote, and recessive models (allele contrast: OR = 1.588, CI: 1.316-1.915). Significant heterogeneity was mainly observed in studies on the G894T polymorphism. No publication bias was detected in all of the variants. The eNOS polymorphisms G894T, 4 VNTR, and T786C were associated with an increased risk for ED. However, these results are still preliminary. Further studies based on different confounders and using a large population size should be conducted to generate more accurate and reliable conclusions.

P-023 eNOS polymorphisms in relation to outcome in advanced HCC patients receiving sorafenib

P-023 eNOS polymorphisms in relation to outcome in advanced HCC patients receiving sorafenib