Endothelin-1 Gene Research Articles

Polymorphism LYS198ASN endothelin-1 gene as a predictor of the development coronary heart disease in patients with chronic obstructive pulmonary disease.

Background and Aims: Among the main systemic manifestations in patients with chronic obstructive pulmonary disease (COPD) are systemic inflammation and endothelial dysfunction. Since heredity is a risk factor for both COPD and coronary heart disease (CHD), the need to include genetic markers in the calculations for predicting the risk of cardiovascular disease in patients with COPD is currently an important part of the study. Single-nucleotide polymorphisms (SNPs) of the endothelin-1 (EDN-1) gene are considered as possible genetic markers of endothelial dysfunction. The aim of the study was to determine the frequencies of alleles and genotypes of the SNPs Lys198Asn of the EDN1 gene in men of Podilskyi region of Ukraine with COPD, including when combined with CHD.

TLR4-Endothelin Axis Controls Syncytiotrophoblast Motility and Confers Fetal Protection in Placental Malaria.

Pregnancy-associated malaria is often associated with adverse pregnancy outcomes. Placental circulatory impairments are an intriguing and unsolved component of malaria pathophysiology. Here, we uncovered a Toll-like receptor 4 (TLR4)-TRIF-endothelin axis that controls trophoblast motility and is linked to fetal protection during Plasmodium infection. In a cohort of 401 pregnancies from northern Brazil, we found that infection during pregnancy reduced expression of endothelin receptor B in syncytiotrophoblasts, while endothelin expression was only affected during acute infection. We further show that quantitative expression of placental endothelin and endothelin receptor B proteins are differentially controlled by maternal and fetal TLR4 alleles. Using murine malaria models, we identified placental autonomous responses to malaria infection mediated by fetally encoded TLR4 that not only controlled placental endothelin gene expression but also correlated with fetal viability protection. In vitro assays showed that control of endothelin expression in fetal syncytiotrophoblasts exposed to Plasmodium-infected erythrocytes was dependent on TLR4 via the TRIF pathway but not MyD88 signaling. Time-lapse microscopy in syncytiotrophoblast primary cultures and cell invasion assays demonstrated that ablation of TLR4 or endothelin receptor blockade abrogates trophoblast collective motility and cell migration responses to infected erythrocytes. These results cohesively substantiate the hypothesis that fetal innate immune sensing, namely, the TRL4-TRIF pathway, exerts a fetal protective role during malaria infection by mediating syncytiotrophoblast vasoregulatory responses that counteract placental insufficiency.

The association of endothelin-1 gene polymorphism and its plasma levels with hypertension and coronary atherosclerosis.

IntroductionEndothelin-1 (ET-1) is the most potent among all vasoconstrictors, and its association with cardiovascular diseases has been reported before. Our aim was to investigate the association of ET-1 plasma level and its gene polymorphisms (rs5370 and rs10478694) with hypertension and coronary atherosclerosis (CA).Material and methodsThis study was carried out on 128 women and 132 men, who were divided into 4 groups: hypertensive without atherosclerosis (H+A–); hypertensive with atherosclerosis (H+A+); non-hypertensive with atherosclerosis (H–A+); and non-hypertensive without atherosclerosis (control group). Endothelin-1 plasma levels were measured by ELISA, and gene polymorphisms were detected by polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) methods. Coronary artery diseases (CAD) were then defined based on angiography data.ResultsThe ET-1 plasma level was significantly higher in the H+A+ group in comparison with the other groups, especially H+A–. Comparing people with CA and those without it, the highest frequency level of the T allele of rs5370 was found in people with CA. Significantly higher frequencies of the 3A allele were detected in hypertensive patients in comparison with non-hypertensive individuals, when analyzing rs10478694.ConclusionsEndothelin-1 plasma level shows a direct association with the risk of CA development. The T allele of rs5370 can be regarded as a risk factor for CA development. The 3A allele of rs10478694 can be associated with the risk of hypertension; therefore, it can be concluded that ET-1 and its gene polymorphisms play an important role in CA development and hypertension observed in the south-eastern populations of Iran.

Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression

Objective: As a distinct cellular signaling model, a receptor crosstalk between G protein-coupled receptors (GPCR) and epidermal growth factor receptor (EGFR) has been demonstrated in various in vitro studies. In addition, recent in vitro studies had focused on the signaling pathways of endothelin-1 (ET-1) in the pathophysiology of cancer. Accordingly, a growing interest in the analysis of the receptor crosstalk between ET-1 receptors and EGFR and functional consequences of EGFR activation of proliferative diseases evoked us to the analysis of this phenomenon in vivo. Materials and Methods: We performed a comparative study between ET-1 transgenic mice and control mice during the late pregnancy (n=7), early lactation (n=6) the mid of lactation (n=10) and involution day 14 (n=7) periods. Hematoxylin and eosin (HE)- stained parallel sections from mammary glands were microscopically examined. The key signal proteins (ETAR, ETBR, ERK1/2, pEGFR) in transactivation of EGFR were analyzed employing Western blot techniques. Genes (amphiregulin, TGFa, EGF, HB-EGF, ADAM 17) known to play an important role in these activities were analyzed using real-time PCR (RT-PCR) techniques. Results: ET-1 transgenic mice exhibited hyperproliferative lesions (lactational hyperplasia) during the middle of the lactation period. Our RT-PCR analyses showed a prominent up regulation of amphiregulin and ADAM 17 in ET-1 transgenic mice. Moreover, we found higher EGFR and ERKs activations in the transgenic mammary glands. Conclusion: This study highlights a causative effect of upregulated ET-1 gene expression on the induction of proliferative lesions via EGFR transactivation in mammary glands. Further, ET-1 overexpression induced an upregulation of amphiregulin and ADAM17 expressions in the transgenic mammary glands. These results suggests that the enhanced ET-1 gene expression and its receptors might have a crucial role in proliferative diseases maintaining EGFR activation.

ERN1 knockdown modifies the impact of glucose and glutamine deprivations on the expression of EDN1 and its receptors in glioma cells.

Objective. The aim of the present investigation was to study the impact of glucose and gluta-mine deprivations on the expression of genes encoding EDN1 (endothelin-1), its cognate receptors (EDNRA and EDNRB), and ECE1 (endothelin converting enzyme 1) in U87 glioma cells in response to knockdown of ERN1 (endoplasmic reticulum to nucleus signaling 1), a major signaling pathway of endoplasmic reticulum stress, for evaluation of their possible implication in the control of glioma growth through ERN1 and nutrient limitations. Methods. The expression level of EDN1, its receptors and converting enzyme 1 in control U87 glioma cells and cells with knockdown of ERN1 treated by glucose or glutamine deprivation by quantitative polymerase chain reaction was studied. Results. We showed that the expression level of EDN1 and ECE1 genes was significantly up-regulated in control U87 glioma cells exposure under glucose deprivation condition in comparison with the glioma cells, growing in regular glucose containing medium. We also observed up-regulation of ECE1 gene expression in U87 glioma cells exposure under glutamine deprivation as well as down-regulation of the expression of EDN1 and EDNRA mRNA, being more significant for EDN1. Furthermore, the knockdown of ERN1 signaling enzyme function significantly modified the response of most studied gene expressions to glucose and glutamine deprivation conditions. Thus, the ERN1 knockdown led to a strong suppression of EDN1 gene expression under glucose deprivation, but did not change the effect of glutamine deprivation on its expression. At the same time, the knockdown of ERN1 signaling introduced the sensitivity of EDNRB gene to both glucose and glutamine deprivations as well as completely removed the impact of glucose deprivation on the expression of ECE1 gene. Conclusions. The results of this study demonstrated that the expression of endothelin-1, its receptors, and ECE1 genes is preferentially sensitive to glucose and glutamine deprivations in gene specific manner and that knockdown of ERN1 significantly modified the expression of EDN1, EDNRB, and ECE1 genes in U87 glioma cells. It is possible that the observed changes in the expression of studied genes under nutrient deprivation may contribute to the suppressive effect of ERN1 knockdown on glioma cell proliferation and invasiveness.

Abstract MP15: Hypoxia and Endothelin-1 in Microglial Cell Activation

Oxidative stress and inflammatory responses play critical roles in hypoxic-ischemic brain injury. Microglial cells are rapidly activated in response to injury and stressful stimuli, including hypoxia. Endothelin-1 (ET-1) is a potent vasoconstrictor that has been associated with cerebrovascular diseases. Hypoxia stimulates endothelial ET-1 production. However, the role of ET-1 in microglia under hypoxia is not clear. The aim of this project was to characterize the effect of hypoxia in a human microglial cell line, HMC3. We induced hypoxia using a chamber (1% O2, 5% CO2, and 92 % N2) at 37 °C for 4h, 24h, and 48h. MUSE Oxidative Stress Assay was performed to measure reactive oxygen species (ROS) formation, ELISA to determine TNF, IL-6, and ET-1 levels, qPCR to measure gene expression of ET-1, and immunofluorescence staining to visualize and compare the presence of ET-1 in hypoxic and control group cells. It was observed that, when compared to normoxic HMC3 cells, hypoxic HMC3 exposure significantly increased the ROS by a factor of 2.5 (p<0.001, n=3), the pro-inflammatory cytokine TNF-α increased 3.8 times (p<0.01, n=4), and IL-6 increased by a factor of 1.6 (p<0.01, n=4). In addition, hypoxia stimulates ET-1 gene expression 5.0-fold (p<0.001, n=4) and increased protein production 1.3 times (p<0.01, n=4). Consequently, treatment with ET-1 increased the amount of ROS, TNF-α, and IL-6 in HMC3 cells by a factor of 1.4 (p<0.05, n=4), 1.6 (p<0.001, n=4), and 1.9 (p<0.05, n=4), respectively. All these events were blocked by ET-1 receptor A (ETRA) antagonist, BQ123. Our results suggest that hypoxic conditions create a cycle of microglial cell activation leading to increased ROS and ET-1 production that further stimulate microglial cells. Thus, we posit that the ET-1 receptor blockade represents a promising therapeutic approach to regulate microglial cell responses in hypoxic-ischemic brain injury.

PLASMA CONCENTRATION OF ENDOTHELIN-1 IN PATIENTS WITH HYPERTENSION ASSOCIATED WITH OBESITY, DEPENDING ON THE LYS198ASN POLYMORPHISM OF THE ENDOTHELIN-1 GENE

Endothelial dysfunction is considered one of the main mechanisms for the further development of arterial hypertension (AH) and its complications, and endothelin-1 (ЕТ-1) plays one of the key roles in this process. Endothelium is drawn into the pathological process at the earliest stages of AH development. ЕТ-1 is currently considered as a marker and predictor of the stage and consequences of AH, chronic heart failure (CHF), coronary heart disease (CHD), in particularly, acute myocardial infarction (MI), heart rhythm disorders, pulmonary hypertension, atherosclerotic vascular injury, target vascular disorders. One factor that may influence the level of ЕТ-1 is the endothelin-1 gene Lys198Asn polymorphism, which is considered by many researchers as a possible genetic marker of AH. However, the effect of this polymorphism on the level of plasma ЕТ-1 level in patients with AH of varying severity in Ukraine is understudied. The basis of this work were the materials of a complete examination of 160 patients with a verified diagnosis of AH I, stage II of 1, 2, 3 degrees (main group) and 110 apparently healthy persons (control group). Patients of the main group were divided into three subgroups: 1st group ­– 75 patients with normal body weight; 2nd group – 48 overweight patients; 3rd group – 37 patients with alimentary obesity. In obese patients, the waist circumference in women was around 103 (96–115) cm, and in men – 108 (105–116) cm, which indicates an abdominal type of obesity in these patients. As a result of the study, it was found that the level of ЕТ-1 is higher in patients with AH who suffer with overweight and obesity as compared with patients with AH and normal body weight. Also, the peptide level depends on the genotype of patients and is higher in AH patients with the genotype Asn198Asn and Lys198Asn as compared to carriers of the genotype Lys198Lys.

Preeclampsia: inflammatory signature of decidual cells in early manifestation of disease

IntroductionPreeclampsia is a pregnancy-specific complication characterized by hypertension in combination with proteinuria and/or various manifestations of multiple organ failure. It is believed that etiology of preeclampsia lies in dysfunction of the placenta and disorder of the maternal-fetal interactions. In preeclampsia decidual membrane, the maternal part of the placenta which normally supports immunological tolerance of the maternal organism to the semi-allogeneic fetus, becomes a site of inflammation. MethodsThe aim of our study was to characterize the phenotype of decidual macrophages and plasma profiles in patients with late- and early-onset preeclampsia as compared with controls (n = 43). Decidual cells were obtained by enzymatic digestion method and characterized by flow cytometry analysis, real-time PCR, bioinformatics analysis, immunohistochemistry, and Western blot. Plasma samples were analyzed by multiplex assay. ResultsThe number of inflammation-associated CD86+ and CX3CR1+ cells was significantly higher in the early-onset preeclampsia while the portion of CD163+ cells was significantly higher among studied groups. We observed significant increase of endothelin-1 gene expression and a significant decrease in eNOS and GNB3 expression and TGFβ relative protein level in decidual cells of the early-onset preeclampsia samples. We also revealed elevation of pro- and anti-inflammatory cytokines in plasma of preeclampsia groups. DiscussionOur findings reflect profound early-onset preeclampsia-associated alterations in the decidua and emphasize the importance of the decidua as a link in the development of preeclampsia.

Effect of Chinese Medicine Xinmaitong on Blood Pressure in Spontaneously Hypertensive Rats.

Objective To investigate the effect of traditional Chinese antihypertensive compound Xinmaitong on blood pressure and vasoactive factors of vasoconstrictor endothelin-1 (ET-1) and vasodilator calcitonin gene related peptide (CGRP) in spontaneously hypertensive rats (SHRs) with early stage hypertension. Methods Twenty male SHRs were randomly divided into two groups: 10 for hypertensive control group and 10 for hypertensive treatment group. In addition, 10 Wistar rats were used as the normal control group without any intervention. SHRs of hypertensive treatment group were orally treated with Xinmaitong, while the hypertensive control group was treated with the normal saline (NS) for a total of eight weeks. The blood pressure in SHRs was examined before and after the end of the eight-week study. After treatment, the rats were killed and the blood samples were collected to measure plasma levels of ET-1 and CGRP by ELISA method, respectively. Meanwhile, the aorta rings were isolated for measuring the mRNA expression of ET-1 and CGRP by PCR. Moreover, the protein levels of ET-1 and CGRP were studied by immunohistochemical. Results Daily oral administration of Xinmaitong resulted in significant fall in the SHRs' blood pressure, including systolic and diastolic blood pressures (SBP and DBP), mean blood pressure (MBP), and pulse pressure (PP). The plasma ET-1 levels were reduced and CGRP increased. In parallel, the mRNA and protein expression of ET-1 were decreased, whereas the mRNA and protein expression of CGRP were enhanced in SHRs treated with Xinmaitong. Conclusion The present study demonstrated for the first time that Xinmaitong leads to the fall in blood pressure of SHRs and that this antihypertensive effect is, at least in part, due to improvement of arterial tone.

Взаимосвязь между полиморфизмом LYS198ASР гена Эндотелин-1 и хронической обструктивной болезнью легких у пациентов узбекской популяции

In the article, in order to identify the role of mutations and polymorphisms of the endothelin-1 gene Lys198Asn in the development of COPD, the authors studied 49 patients with an established diagnosis of COPD. The control group consisted of 46 apparently healthy patients, comparable with the main group in terms of age and sex. The study of mutations and polymorphism of the endothelin-1 gene Lys198Asn was carried out by PCR, statistical analysis was carried out using the statistical software OpenEpi, Version 2.9. As a result, it was found that the heterozygous Lys / Asp genotype of the endothelin-1 gene Lys198Asn was found in the COPD group 1.25 times more often than in the control group. It was found that the mutational genotype Asp / Asp - was found in the COPD group 1.9 times more often than in the control group (RR 1.9, OR - 2.3; χ2 = 0.4), which indirectly shows the significance of changes in this gene in the development of COPD, and its course. The influence of the presence of a genotypic predisposition to endothelial dysfunction with its phenotypic manifestations was evaluated.

NOD2 induces VCAM-1 and ET-1 gene expression via NF-κB in human umbilical vein endothelial cells with muramyl dipeptide stimulation.

Endothelial dysfunction is involved in various aspects of vascular biology and different stages of cardiovascular diseases (CVDs). Nucleotide-binding oligomerization domain-containing protein (NOD)2, apivotal innate immune receptor for muramyl dipeptide (MDP), has been reported to be acentral regulator in CVDs. Previously, we reported that NOD2 played aleading role in MDP-triggered oxidative stress in endothelial cells (ECs). However, whether NOD2 participates in the regulatory mechanism of vascular cell adhesion molecule‑1 (VCAM-1) and endothelin‑1 (ET-1) expression was not elucidated. Human umbilical vein endothelial cells (HUVECs) were stimulated with MDP for 12 h. mRNA expression of VCAM‑1 and ET‑1 was detected using real time polymerase chain reaction (PCR). Scrambled control small interfering RNA (siRNA) and NOD2 siRNA were transfected into HUVECs using Lipofectamine 2000 reagent (Invitrogen, Waltham, MA, USA). Furthermore, pyrrolidine dithiocarbamate was adopted to investigate the effect of nuclear factor κB (NF-κB) on NOD2-mediated VCAM‑1 and ET‑1 gene expression in MDP-treated HUVECs. Data showed that MDP significantly increased VCAM‑1 and ET‑1 mRNA expression, which was dependent on NOD2. In addition, NF-κB inhibition suppressed NOD2-mediated gene expression of VCAM‑1 and ET‑1. Collectively, we confirmed NOD2 aggravated VCAM‑1 and ET‑1 gene expression through NF-κB in HUVECs treated with MDP.

Correlations of endothelin-1 gene polymorphisms and hypertensive intracerebral hemorrhage.

The aim of this study was to investigate the correlations of endothelin-1 (ET-1) gene polymorphisms with the occurrence of hypertensive intracerebral hemorrhage (HICH). In this case-control study, 100 HICH patients and 100 controls with matched race, age and gender were enrolled as research subjects. Single nucleotide polymorphisms (rs1920453, rs1022436 and rs1035627) in the promoter region of ET-1 gene were typed via conformational difference gel electrophoresis. Whether the distribution frequency of ET-1 genotypes conformed to Hardy-Weinberg equilibrium was evaluated by chi-square test. The correlations of different gene polymorphisms and alleles in the promoter region of ET-1 gene with the occurrence of HICH were analyzed. Furthermore, the associations of rs1920453 polymorphism in the promoter region of ET-1 gene with neurological deficit scores and laboratory parameters of HICH patients were explored. It was found that ET-1 gene polymorphisms (rs1920453, rs1022436 and rs1035627) conformed to Hardy-Weinberg equilibrium (p>0.05). Gene-based association analysis indicated that only rs1920453 polymorphism and alleles were correlated with the occurrence of HICH (p<0.05). However, rs1022436 and rs1035627 polymorphisms and alleles had no association with HICH (p>0.05). Additionally, NIHSS score and high-density lipoprotein cholesterol level were prominently higher in HICH patients with CG and GG genotypes of ET-1 gene polymorphism rs1920453 than those in patients with CC genotype (p<0.05). Rs1920453 in the promoter region of ET-1 gene is correlated with the occurrence of HICH.

Epigenetic Changes and Cardiovascular Risks among Workers Occupationally Exposed to Iron and Zinc

Introduction: Several metals such as Iron and Zinc were found at high concentration in foundry particulate matter and demonstrated to have procoagulant effects, these effects may occur through epigenetic changes of pro-inflammatory genes. So, Iron and Steel workers are at a high risk for cardiovascular diseases. Aim of work: Evaluation of the risk of thrombosis and cardiovascular diseases among individuals occupationally exposed to Iron and Zinc. Materials and methods: A descriptive cross sectional comparative study was performed on 60 persons working in Iron and Steel factory and 60 subjects used as control group with no history of occupational exposure to Fe or Zinc. All study population was subjected to personal interview with specially designed questionnaire. Serum Iron and Zinc levels together with Endogenous thrombin potential (ETP) test were measured. Assessment of methylated DNA of Endothelin-1 (EDN1) and Nitric-oxide synthase-3 (NOS3) genes were performed. Results: the current study showed highly statistically significantincrease of serum Iron, Zinc levels and percentage of ETP among exposed group when compared to the control with Mean ± SD 125.6±22.9, 110.9±19.2,168±0.5 vs 63.6±15.3, 42.5±7.2, and 102.22±12.36 respectively. There was also a significant decrease of methylated DNA of EDN1and NOS3 genes among exposed group with Mean ± SD 0.71±0.3, 0.75±0.3 versus 1.51±1.01,4.09±0.68 respectively among the control group. Serum levels of Iron and Zinc and percentage of ETP were negatively correlated with methylated DNA of NOS3 and EDN1 genes r= -0.304, r=-0.450, r=-0.259, r= -0.787, r= -0.866 and r= -0.618 respectively (p value <0.005), while positive correlation were detected between Iron and Zinc levels with ETP (r= 0.692 and r=0.625). It was found that Iron, Zinc and NOS3 are determinants for END1 while the latter is the only predictor for NOS3. Conclusion: The risk of thrombosis and cardiovascular diseases were related to occupational exposure to high levels of Iron and Zinc. So, regular wearing of good quality’s personal protective equipment, especially masks and gloves, is highly recommended to decrease exposure to these metals.

Knockout of the circadian clock protein PER1 results in sex-dependent alterations of ET-1 production in mice in response to a high-salt diet plus mineralocorticoid treatment.

Previously, we showed that global knockout (KO) of the circadian clock transcription factor PER1 in male, but not female, mice fed a high-salt diet plus mineralocorticoid treatment (HS/DOCP) resulted in nondipping hypertension and decreased night/day ratio of sodium (Na) excretion. Additionally, we have shown that the endothelin-1 (ET-1) gene is targeted by both PER1 and aldosterone. We hypothesized that ET-1 would exhibit a sex-specific response to HS/DOCP treatment in PER1 KO. Here we show that male, but not female, global PER1 KO mice exhibit a decreased night/day ratio of urinary ET-1. Gene expression analysis revealed significant genotype differences in ET-1 and endothelin A receptor (ETA) expression in male, but not female, mice in response to HS/DOCP. Additionally, both wild-type and global PER1 KO male mice significantly increase endothelin B receptor (ETB) expression in response to HS/DOCP, but female mice do not. Finally, siRNA-mediated knockdown of PER1 in mouse cortical collecting duct cells (mpkCCDc14) resulted in increased ET-1 mRNA expression and peptide secretion in response to aldosterone treatment. These data suggest that PER1 is a negative regulator of ET-1 expression in response to HS/DOCP, revealing a novel mechanism for the regulation of renal Na handling in response to HS/DOCP treatment.

Elevated circulating endothelin-1 as a potential biomarker for high-risk COVID-19 severity

&lt;img src=” https://s3.amazonaws.com/production.scholastica/article/13525/large/prnano_512020_ga.jpg?1593450067”&gt; There is a disproportionately higher rate of adverse outcomes in coronavirus disease 2019 (COVID-19) patients of male sex, select ethnicity, and individuals with obesity and those that tend to have endothelial dysfunction (e.g., hypertensives, diabetics and individuals with coronary heart disease and respiratory system diseases). Endotheliitis across vascular beds of multiple organs, thrombosis and ischaemia are among common pathological features of severe COVID-19 cases. Endothelin-1 (ET-1) is the most potent vasoconstrictor of the human cardiovascular system and a culprit of endothelial dysfunction. Elevated circulating ET-1 levels are a predictor of cardiovascular disease status and have been correlated with racial/ethnic differences in microvascular and macrovascular diseases severity and prognosis as well as with old age associated endothelial dysfunction. Here, we propose elevated circulating ET-1 levels as a plausible biomarker and prognostic tool in predicting individuals at high risk of developing severe COVID-19. In addition to this, we also propose ET-1 gene variants and expression patterns might also cause predisposition for an increased risk of severe acute respiratory syndrome coronavirus 2 infection severity in some individuals and/or populations. READ THE ARTICLE (https://doi.org/10.33218/001c.13525)

Association of +138I/D and Lys198Asn Polymorphisms in the Endothelin-1 Gene with Early Onset of Coronary Artery Disease among the Chinese Han Population.

BackgroundHuman endothelin-1 (ET-1) gene polymorphism is closely associated with coronary artery disease (CAD). This study aimed to investigate the association of 2 single-nucleotide polymorphisms (SNPs), +138 I/D and Lys198Asn) of the ET-1 gene,with early onset of CAD in Han Chinese patients. We investigated the effects of Lys198Asn polymorphism on ET-1 protein expression upon stimulation with pro-inflammatory factors.Material/MethodsGenotyping of the 2 SNPs +138 I/D and Lys198Asn was performed in 88 early-onset CAD patients (≤55 years for males; ≤60 years for females) and 52 healthy control participants using a polymerase chain reaction direct sequencing method. The association of the 2 SNPs was analyzed with SPSS 17.0 software. Western blotting was performed to assess the effects of ET-1 polymorphisms on ET-1 protein expression upon tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and lipopolysaccharide (LPS) stimulation in HEK-293T cells.ResultsFisher’s exact test showed that the T allele (odds ratio [OR]=3.38, P=0.02) and GT/TT genotype (OR=3.76, P=0.02) of the ET-1 gene Lys198Asn were associated with increased early-onset CAD risk. Multivariate logistic regression analysis showed smoking was the single independent variable related to early-onset CAD (P<0.05). An increase of ET-1 protein levels in cells transfected with Asn198 plasmid was seen upon TNF-α or IL-6 stimulation.ConclusionsT allele frequency in Lys198Asn loci might be associated with the pathogenesis of early-onset CAD. T-variant might contribute to early-onset CAD by upregulating ET-1 expression upon inflammatory cytokines stimulation, and smokers who have the T allele might be vulnerable to CAD in the Chinese population.

Evaluate the gene expression of TPT1, EDN3, and ANO7 in prostate cancer tissues and their relation with age, tumor stage and family history

BackgroundNowadays, most important prostate cancer (PCa) screening tests might include prostate-specific antigen (PSA) test and digital rectal exam (DRE). In present study we are tried to discover a new way to monitoring and screening PCa patients. To receive this propose, we evaluate of genes expression in prostate tumor samples that including tumor protein translationally controlled 1(TPT1), endothelin-3 (EDN3), and anoctamin-7 (ANO7). MethodsThe biopsy-proven PCa treated at Shahid Akbar Abadi Hospital of 40 patients with were enrolled, and extracted DNA was introduced to real-time PCR. All patients are checked their smoking habit, family history of prostate cancer encounter and stages and grades of their PCa by TNM (tumor, node, metastasis) staging system. ResultsAccording to our results, there is not any significant correlation between age average of PCa and control groups (P-value >.05). Moreover, we can't approve any correlation between smoking and prostate cancer disease. Real-time PCR results of genes expression of TPT1, EDN3, and ANO7 are showed that there is an increasing in these genes expression in PCa group. With pay attention to Mann-Whitney test results, there isn't any significant relation between PCa and existence of person with PCa in their family (P-value >.05). Interestingly, T4N1M1 just showed 5.7% frequency among all PCa samples but all of them are both family history and smoking positive. ConclusionsAccording to the above, we are approved a potential of monitoring and screening PCa by targeting TPT1, EDN3, and ANO7 genes expression approach.

Potential correlation between EDN1 gene polymorphisms with preeclampsia.

To explore the potential correlation between endothelin 1 (EDN1) gene polymorphisms with preeclampsia (PE). The single nucleotide polymorphisms (SNPs) of 248 PE patients and 232 healthy controls were genotyped by Polymerase Chain Reaction (PCR). The possible association between EDN1 polymorphisms and PE was revealed through the t-test and the Chi-square test. PE risk was significantly correlated with the C allele of polymorphism rs5370 in EDN1. The polymorphism rs5370 in EDN1 was remarkably associated with the onset of severe PE, rather than mild PE. The markedly increased risk of early-onset PE was related to the C allele of polymorphism rs5370 in EDN1, while no significant difference in the allele frequency of polymorphism rs1800541 was detected between the PE group and the control group. In the co-dominant model, the CC genotype of polymorphism rs5370 in EDN1 was associated with the increased PE risk. PE risk in the population carrying TC genotype was 1.59 times higher than those with TT/CC genotype, while polymorphism rs1800541 had no apparent association with PE risk. In the severe PE group, there was an evident difference in the genotype frequency between the dominant and over-dominant models of polymorphism rs5370. In the recessive model, the raised risk of early-onset PE was notably correlated with the TT/CC genotype compared with that of TT genotype. However, no evident association with the genotype frequency of polymorphism rs1800541 was observed between PE patients and controls. EDN1 gene polymorphism rs5370 is correlated with the increased risk of PE.

Endothelin-1 rs9296344 associates with the susceptibility of childhood primary nephrotic syndrome.

BackgroundRecently, the rs5370 single nucleotide polymorphisms (SNPs) of Endothelin‐1 (EDN1) showed association with the susceptibility of childhood primary nephrotic syndrome (CPNS). This study aims to investigate potential relationships between other EDN1 SNPs and CPNS.MethodsSeven SNPs (rs5370, rs10478723, rs1476046, rs1800541, rs2070698, rs2071942, and rs9296344) of the EDN1 gene were genotyped in 579 CPNS patients and 586 age‐matched healthy children. Then, we analyzed potential associations of the six SNPs with susceptibility of CPNS by using rs5370 as a conditional variant in a logistic regression model. SNP‐SNP interaction analysis was performed to investigate the joint effects of the seven SNPs in the pathogenesis of CPNS.ResultsIndependent with rs5370, only rs9296344 significantly associated (T vs C, odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.57‐0.88, P = .001) with the susceptibility of CPNS. Meanwhile, no joint effect among the analyzed seven SNPs was discovered in this study.ConclusionsThis study discovered that C allele of rs9296344 on EDN1 is a novel independent risk factor for CPNS.

Genetic Relationship Between Endothelin-1 Gene Polymorphisms and Intracerebral Hemorrhage Among Chinese Han People.

BackgroundThe goal of the present study was to determine whether endothelin-1 (EDN1) variants are associated with intracerebral hemorrhage (ICH) risk among Chinese Han people.Material/MethodsThe genotyping of EDN1 rs5370 and rs6458155 polymorphisms were conducted in 154 ICH patients and 168 healthy controls using polymerase chain reaction (PCR) and sequencing. Deviation for genotype frequencies in controls from Hardy-Weinberg equilibrium (HWE) was assessed. The genotype and allele distribution of EDN1 polymorphisms was checked via χ2 test between 2 groups. Strength of the association between EDN1 polymorphisms and ICH risk is presented by odds ratio (OR) and 95% confidence interval (95% CI).ResultsGenotype distribution for rs5370 and rs6458155 polymorphisms in the control group both conformed to HWE (P>0.05). Only CC genotype and C allele frequencies of rs6458155 between ICH patients and healthy individuals were significantly different (P=0.025; P=0.043), indicating rs64581255 is associated with increased ICH onset (OR=2.214, 95% CI=1.009–4.461; OR=1.389, 95% CI=1.010–1.910). When adjusted by confounding factors, the significant correlations still existed between 2 groups (P=0.028, adjusted OR=2.217, 95% CI=1.092–4.500; P=0.046, adjusted OR=1.386, 95% CI=1.005–1.910).ConclusionsEDN1 rs6458155 polymorphism may be a risk factor of ICH among Chinese Han people.