Endothelin-1 Gene Polymorphisms Research Articles

Association of Genetic polymorphisms of EDN1 gene and Endothelin-1 level in patients with type 2 diabetes mellitus in the Jordanian population

Endothelin-1 (ET-1) is one of the most potent vasoconstrictors, encoded by the endothelin-1 (EDN1) gene. It has been shown to play an important role in different diseases including Diabetes Mellitus (DM). Various single nucleotide polymorphisms (SNPs) in the EDN1 gene are related to microvascular complications of type 2 diabetes mellitus (T2DM) such as retinopathy, neuropathy and nephropathy. This study aims to determine the association between two selected EDN1 gene polymorphisms (rs2071942 G > A, rs5370 G > T) and T2DM in the Jordanian population, also to measure the level of ET-1 in T2DM. The samples were collected from the National Center of Diabetes, Endocrinology, and Genetics- Amman, Jordan, including 97 patients with T2DM and 80 healthy individuals. PCR-RFLP was used for SNPs genotyping. ET-1 level was determined using IQELISA kits. The univariate analysis for both SNPs didn't show statistically significant differences in the genotype or allele frequencies among T2DM cases as well as in controls. The same results were obtained regarding ET-1 concentration. The subgroup analysis by sex showed that the genotype and allelic frequencies of rs5370, rs2071942 G/A polymorphisms were not significantly different in males and females. Multivariate Analysis adjusted for various confounders didn't express statistical significance difference for occurrences of both SNPs. However, height and gender showed to be significant risk factors for occurrences of heterozygote alleles in both SNPs. On the other hand, the duration of diabetes has appeared to be related to the recessive allele in rs5370.

THE ASSOCIATION OF PRE-TAVI HOSPITALIZATIONS ON THE SHORT-TERM OUTCOMES AFTER TAVI

The female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males.We aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ETA) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD).We compared prevalence of ET-1 gene (Lys198Asn) and ETA gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls.The presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p =0.007 and OR 2.39; p =0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p =0.047 and OR 2.26; p =0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p =0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p =0.018) were independent predictors of development of PH in females.ET-1 and ETA gene polymorphisms were more prevalent in females than males in PH-MVD signifying that females with rheumatic heart disease may be more susceptible to develop PH.

Potential role of eNOS and EDN-1 gene polymorphisms in the development and progression of retinopathy of prematurity

The aim of this study was to investigate the association between selected polymorphisms of nitric oxide synthetase (eNOS) and endothelin-1 (EDN-1) with the occurrence and progression of retinopathy of prematurity (ROP). A prospective study was conducted on 90 preterm infants (44 female), comparing 39 cases with ROP and 51 controls without ROP. Patients who developed ROP were further divided into two subgroups—those with spontaneous regression of the disease and those with ROP requiring treatment. We found that preterm infants with TT genotype eNOS 894G > T had a 12.8-fold higher risk of developing ROP requiring treatment (p = 0.02). Our results showed that allele T of eNOS894G > T polymorphism was significantly more prevalent in ROP patients requiring treatment (p = 0.029). We also investigated preterm infants with TC genotype eNOS − 786 T > C and found an 8.8-fold higher risk developing of ROP requiring treatment (p = 0.021). Our results didn’t show any association between EDN-1 5665G > T polymorphism and ROP development. The eNOS polymorphisms appears to influence incidence of ROP requiring treatment in preterm infants. Future research on single nucleotide polymorphisms may provide important information about the pathogenetic mechanisms underlying the development of ROP.

Endothelin-1 gene polymorphism (G8002A) and endothelial monocyte-activating polypeptide II: Role in vascular dysfunction in pediatric patients with β-thalassemia major.

Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, stimulates production of reactive oxygen species. Endothelial monocyte-activating polypeptide-II (EMAP-II) is a multifunctional polypeptide. To assess ET-1 gene polymorphism (G8002A) in pediatric patients with β-thalassemia major (β-TM) as a potential genetic marker for vascular dysfunction and its possible relation to EMAP II, oxidative stress and vascular complications. β-TM patients (n=95) without symptomatic cardiac or renal disease were compared with 95 healthy controls. Markers of hemolysis, serum ferritin, urinary albumin-to-creatinine ratio, serum EMAP II, malondialdehyde (MDA) and antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase and catalase were measured. ET-1 gene polymorphism (G8002A) was determined using polymerase chain reaction‑restriction fragment length polymorphism. β-TM patients had significantly higher EMAP II than healthy controls. EMAP II was significantly higher among patients with cardiac disease, pulmonary hypertension (PH) risk, nephropathy, poor compliance to therapy and ferritin≥2500μg/L. There were significant correlations between EMAP II and transfusion index, LDH, ferritin and oxidative stress markers. The AA genotype of ET-1 gene polymorphism (G8002A) was significantly higher among β-TM patients than controls. The number of patients with cardiac disease, PH risk or nephropathy was significantly higher among AA genotype compared with GG and GA genotypes. Lactate dehydrogenase (LDH), serum ferritin, EMAP II, MDA, SOD and GPx were significantly higher in AA genotype. ET-1 gene polymorphism (G8002A) could be a possible genetic marker for prediction of increased susceptibility to cardiopulmonary and renal complications among pediatric patients with β-TM.

Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease

IntroductionThe female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males. AimWe aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ETA) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD). MethodsWe compared prevalence of ET-1 gene (Lys198Asn) and ETA gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls. ResultsThe presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p =0.007 and OR 2.39; p =0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p =0.047 and OR 2.26; p =0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p =0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p =0.018) were independent predictors of development of PH in females. ConclusionsET-1 and ETA gene polymorphisms were more prevalent in females than males in PH-MVD signifying that females with rheumatic heart disease may be more susceptible to develop PH.

Association of Endothelin-Converting Enzyme and Endothelin-1 Gene Polymorphisms with Essential Hypertension in Malay Ethnics.

Objectives Endothelin-1 (ET-1), the most potent endogenous vasoconstrictor, generated by enzymatic cleavage catalyzed by an endothelin-converting enzyme (ECE), plays a significant role in the regulation of hypertension. Methods This study investigates the effect of endothelin-1 (Lys198Asn/rs5370) and ECE (rs212526 C/T) gene polymorphisms with essential hypertension (EH) among Malay ethnics. To determine the association of gene polymorphism, 177 hypertensives and controls (196) were genotyped using Taqman method. Results A significant difference was observed in ET-1 rs5370 and ECE rs212526 gene polymorphisms between EH and control subjects (P < 0.001). A significantly high body mass index (BMI), waist-to-hip ratio, fasting plasma glucose, hemoglobin A1c, systolic and diastolic blood pressure, and lipid profiles were observed among the EH patients when compared to controls (P < 0.05). Moreover, T allele (rs5370) carriers in males have a high risk for EH. There was no significant association between gender in ECE C/T polymorphisms (P > 0.05). Conclusion Based on our result, it is evident that the T allele of ET-1 rs5370 polymorphism and C allele of ECE rs212526 have a significant genetic risk factor in EH among Malay subjects, and BMI and age are associated with hypertension.

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.

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.

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.

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.

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.

Association between Lys198Asn polymorphism of endothelin-1 gene and ischemic stroke: A meta-analysis.

BackgroundEndothelin (ET)‐1 is a potent vasoconstrictor peptide produced by endothelial cells and associated with vascular dysfunction and cardiovascular disease. Lys198Asn is a single‐nucleotide polymorphism (SNP) of gene encoding ET‐1 (EDN1). It is hypothesized that it might have a role in altering ET‐1 and ultimately leading to vascular dysfunction and ischemic stroke. We therefore conducted a meta‐analysis to investigate the association between Lys198Asn polymorphism of EDN1 gene and susceptibility of ischemic stroke.MethodsThis meta‐analysis was conducted according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. We searched PubMed, Google Scholar, Embase, Web of Science, J‐STAGE, and China National Knowledge Infrastructure (CNKI) for relevant studies. The association between Lys198Asn polymorphism and ischemic stroke susceptibility was evaluated by calculating the pooled ORs and 95% CIs.ResultsOur analysis included 1,291 cases and 2,513 controls. Meta‐analysis established a significant association between Lys198Asn SNP of EDN1 gene and ischemic stroke when assuming either recessive model (OR: 1.30; 95% CI: 1.02–1.65; p = .03; I 2 = 41%) or dominant model (OR: 1.48; 95% CI: 1.24–1.76; p < .001; I 2 = 61%). There was no evidence of publication bias in either of the recessive model (Egger test: p = .23; Begg test: p = .85) or dominant model (Egger test: p = .79; Begg test: p = .85). A subgroup analysis based on subtypes of ischemic stroke showed that Lys198Asn SNP was only associated with large vessel infarction but not with lacunar infarction caused by small vessel disease. A subgroup analysis based on ethnicity revealed that the Lys198Asn polymorphism of the EDN1 gene was associated with ischemic stroke only in Caucasians.ConclusionsThe present meta‐analysis suggests that Lys198Asn polymorphism of EDN1 gene is associated with an increased risk for ischemic stroke.

Endothelin-1 gene polymorphism in Egyptian patients with vitiligo

Objective The aim was to investigate the association between endothelin-1 (ET-1) gene polymorphism and vitiligo occurrence or increased vitiligo risk in Egyptian population. Background ET-1 is a keratinocyte-derived cytokine, which also has been defined as a strong mitogen and melanogen for human melanocytes and a potent stimulant of melanocyte proliferation, melanogenesis, and migration, implying a link with vitiligo. Patients and methods This study was conducted on 60 female patients with vitiligo. Their ages ranged from 6 to 70 years Overall, 54 cases presented with nonsegmental vitiligo and six cases presented with segmental vitiligo. Moreover, 40 age-matched and sex-matched apparently healthy volunteers with no past, present, or family history of vitiligo were included as a control group. Every case and control underwent detection of genotyping of ET-1 by restriction fragment length polymorphism-PCR. Results AA genotype of ET-1 was significantly associated with cases. It increases the risk of vitiligo by 15.9 folds. GA genotype was prevalent in 36.7% of cases. It increases the risk of vitiligo by 3.3 folds. Conclusion There is an association between ET-1 gene polymorphism and vitiligo occurrence.

Association between polymorphism of lys198asn endothelin-1 gene and endothelin-1 plasma level in javanese obesity population

Background: Endothelin-1 plays a role as a vasoconstrictor and also inhibits the expression of adiponectin in obesity. The Lys198Asn polymorphism of the endothelin-1 gene will increase the level of endothelin-1 plasma and increase the risk factor of obesity.&#x0D; Objective: In this study, we investigated the relationship between Lys198Asn polymorphism of endothelin-1 gene and endothelin-1 plasma level among individuals with obesity in Javanese population.&#x0D; Method: This study was conducted on 61 obese subjects and 65 control subjects. All subjects were measured for anthropometrics and endothelin-1 plasma level by ELISA (Enzyme-linked Immune Sorbent Assay). The polymorphism of Lys198Asn of ET-1 (Endothelin-1) was screened by using PCRRFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism).&#x0D; Results: TT genotype was a risk factor of obesity (OR 5.344 CI=95% 1.77-16.16) compared with GG genotype. Levels of endothelin-1 plasma were higher in obese subjects than that of control subjects (p=0.013), with TT genotype having the highest endothelin-1 plasma level (p&lt;0.001).&#x0D; Conclusion: The Lys198Asn polymorphism of endothelin-1 gene plays a role in increasing endothelin-1 plasma levels and is risk factors of obesity.&#x0D; Bangladesh Journal of Medical Science Vol.18(1) 2019 p.46-49

Genetic susceptibility of five tagSNPs in the endothelin-1 (EDN1) gene to coronary artery disease in a Chinese Han population.

Endothelin-1 (ET-1) plays important roles in endothelial dysfunction, vascular physiology, inflammation, and atherosclerosis. Nonetheless, the role of ET-1 (EDN1) gene variants on coronary artery disease (CAD) risk remains poorly understood. The aim of the present study was to evaluate the role of EDN1 gene polymorphisms on individual susceptibility to CAD. We genotyped five tagSNPs (single-nucleotide polymorphisms) (rs6458155, rs4145451, rs9369217, rs3087459, and rs2070699) within EDN1 gene in 525 CAD patients and 675 control subjects. In a multivariate logistic regression analysis, we detected an association of rs6458155 in EDN1 gene with the CAD risk; compared with the TT homozygotes, the CT heterozygotes (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.02–2.29, P=0.040) and the CC homozygotes (OR = 1.55, 95% CI = 1.01–2.36, P=0.043) were statistically significantly associated with the increased risk for CAD. A similar trend of the association was found in dominant model (OR = 1.53, 95% CI = 1.05–2.25, P=0.029). Consistently, the haplotype rs6458155C-rs4145451C containing rs6458155 C allele exhibited the increased CAD risk (OR = 1.22, 95% CI = 1.03–1.43, and P=0.018). In addition, CT genotype of rs6458155 conferred the increased plasma ET-1 levels compared with TT genotype (P<0.05). No association of the other four tagSNPs in EDN1 gene with CAD risk was observed. In conclusion, our study provides the first evidence that EDN1 tagSNP rs6458155 is associated with CAD risk in the Chinese Han population, which is probably due to the influence of the circulating ET-1 levels.

Endothelin-1 Gene Polymorphisms rs5370, rs1476046, and rs3087459 are not Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus.

Diabetic nephropathy (DN) is a major microvascular complication of type 2 diabetes mellitus (T2DM). Several lines of evidence implicate the endothelin (ET) system in the pathophysiology of DN. The aim of the present study was to analyze if genetic polymorphisms of the ET-1 (EDN1) gene affect susceptibility to DN in Caucasians with T2DM. The study population consisted of 651 Caucasian subjects with T2DM of more than 10 years' duration: 276 patients with DN (cases) and 375 patients without evidence of DN (controls). Polymorphisms in ET-1 (EDN1) gene, rs5370, rs1476046, and rs3087459, were studied. Genotype distributions of the studied polymorphisms showed no significant difference between cases and controls. We provide evidence that the rs5370, rs1476046, and rs3087459 polymorphisms of EDN1 gene are not risk factors for DN in Caucasians with T2DM.

Is endothelin gene polymorphism associated with postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting?

Background:The mechanism of development of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) has not been clearly defined, and the involvement of multiple factors such as advanced age, withdrawal of β-blockers, inadequate atrial protection, and electrolyte imbalance, particularly hypomagnesemia has been documented by several authors. Despite all the available pharmacologic prophylaxis, incidence of AF still remains high in this group of patients. This unexplained cause could be genetic inheritance of endothelin-1 (ET-1) gene which is thought to have a pro-arrhythmogenic effect.Aim:This study aims to investigate the relationship between plasma ET-1 concentrations, ET-1 gene polymorphisms in loci -1370 T/G, -134 (3A/4A) Ins/del, Lys198Asn (G/T), and occurrence of AF in patients undergoing CABG.Methodology:Ninety-eight nonrelated, nondiabetic patients over a period of 4 years undergoing routine CABG were selected for the present study. All patients were genotyped for three single nucleotide polymorphisms (SNPs) in loci -1370 T/G, -134 (3A/4A) Ins/del, and Lys198Asn (G/T) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using an ET immunoassay.Results:Plasma ET-1 concentrations were higher in AF+ group (P = 0.001) as compared to AF− group. The allele frequencies between AF+ and AF− group were significantly different only with respect to the Lys198Asn (G/T) SNP of the ET-1 gene.Conclusion:The study described the possible correlation of polymorphism of ET gene in CABG population from India. The ET-1 gene might play a disease-modifying role in atrial fibrillation.

Association of endothelin-1 gene polymorphisms with essential hypertension in a Chinese population.

Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor and is involved in several vascular disorders such as hypertension. Its strong interaction with other vasoactive hormone systems suggests that the ET-1 gene (EDN1) is a potential candidate molecule that influences the risk of developing hypertension. Recently, two single nucleotide polymorphisms in EDN1 have been reported to be associated with hypertension: Lys198Asn and 3A/4A (-134delA) located in the 5'-untranslated region. To determine the association of these two polymorphisms with hypertension, we genotyped patients and controls (N = 537) and compared the allele and genotype frequencies between groups. There was no significant difference in the genotype frequencies of these two polymorphisms between healthy controls and hypertension patients. Although previous reports have revealed a significant interaction between the END1 Lys198Asn (G/T) polymorphism and body mass index in association with hypertension, no such relationship was observed in the present study. Further, we compared blood pressure among hypertensive subjects and observed that neither systolic nor diastolic blood pressure was significantly associated with variations in the genotypes of the two single nucleotide polymorphisms. In summary, these two END1 polymorphisms do not appear to affect the development of hypertension in the Chinese population.

Ratio of Endothelin-1 and C-Type Natriuretic Peptide Concentrations in Men with Hypertensive Disease of Different Severity. The Regulatory Role of Polymorphism of the Endothelin-1 Gene

Despite overall effort hypertensive disease (HD) is one of the most significant health and social problem. Essential hypertension is believed to be a multifactorial disease and polymorphism of genes that may be responsible for the regulation of blood pressure plays the key role in it. The least explored in this regard is single nucleotide polymorphism of ET-1 leading to the replacement of the amino acids of lysine (Lys) to asparagine (Asn) at position of 198th polypeptide chain (Lys198Asn).The objective of the research was to improve diagnosis of HD severity determining plasma concentration of ET-1, C-type natriuretic peptides (CNP) and the coefficient of CNP/ET-1 in patients with different genotypes of ET-1 gene.Materials and methods. The study involved 79 men without cardiovascular diseases (control group), 62 men with II stage HD and 50 men with HD complicated by chronic heart failure (CHF) II-III classes according to NYHA Classification. All patients were representative by age. Genotyping of ET-1 gene was conducted using polymerase chain reaction. ET-1 concentration in plasma was determined using ELISA method.Results. Lys/Lys genotype of ET-1 gene was found to occur in 65.82% of men in the control group, carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) constituted 34.18%, Lys allele was observed in 79.75% of cases, Asn allele was detected in 20.25% of men. Among patients with II stage HD Lys/Lys genotype of ET-1 gene was observed in 56.45% of cases, the carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) occurred in 43.55% of patients, Lys allele was found in 73.39% of cases, Asn allele was observed in 26.61% of patients. Among men with HD and CHF IIA genotype Lys/Lys was found in 66.00% of cases, carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) was observed in 34.00% of patients, Lys allele was detected in 80.00% of cases, Asn allele was observed in 20.00% of cases. The men from the control group, patients with II stage HD and patients with HD and CHF as the carriers of Asn allele were found to have significantly higher plasma levels of ET-1 (2.53±0.12 fmol/ml, 13.90±0.22 fmol/ml and 14.07±0.18 fmol/ml, respectively) and CNP (2.98±0.08 pmol/ml, 5.90±0.11 pmol/ml and 5.93±0.18 pmol/ml, respectively) in comparison with homozygous carriers of Lys genotype (ET-1constituted 1.41±0.05 fmol/ml, 11.58±0.23 fmol/ml and 0.08±12.89 fmol/ml, respectively, CNP constituted 2.02±0.29 pmol/ml, 4.68±0.12 pmol/ml and 4.88±0.09 pmol/ml, respectively). According to the analysis of the obtained data, coefficient of CNP/ET-1 (0.40±0.003 c.u. and 0.38±0.006 c.u., respectively) and Asn allele (0.42±0.004 c.u. and 0.42±0.007 c.u., respectively) was significantly lower in patients with II stage HD and patients with HD and CHF as the carriers of Lys/Lys genotype in comparison with the control group (1.4±0.04 c.u. and 1.22±0.05 c.u., respectively). Carriers of Asn allele in the control group had significantly lower coefficient of CNP/ET-1 than genotype Lys/Lys carriers. However, the difference in the coefficient of CNP/ET-1 was not observed in patients with HD.Conclusions. Lys/Lys genotype and Lys allele of ET-1 gene were found to dominate among control group and patients with HD of different severity. Plasma concentration of ET-1, CNP were significantly higher and coefficient of CNP/ET-1 was lower in men with II stage HD and HD complicated by CHF than in men without cardiovascular diseases in case of all ET-1 gene genotypes. The carriers of Asn allele of ET-1 gene had significantly higher plasma levels of ET-1 and CNP in each study group.

Endothelin-1 Gene Polymorphism and Its Level Predict the Risk of Venous Thromboembolism in Male Indian Population.

Genes related to endothelial function are responsible for the regulation of vascular functions. The aim of this study is to investigate whether endothelial gene-associated polymorphism and their plasma levels can be used to predict the risk for venous thromboembolism (VTE). We studied 133 patients with VTE and 164 healthy controls. Endothelin (EDN) G8002A, EDN T1370G, EDN 3A/4A, eNOSG894T, angiotensin-converting enzyme I/D, vascular endothelial growth factor C936T, and endothelial cell protein C receptor A6936G polymorphism was genotyped by restriction fragment length polymorphism. Plasma levels of endothelin 1 (EDN1), endothelial nitric oxide synthase, and angiotensin-converting enzyme were measured by enzyme-linked immunoassay kit. The genotype and allele frequency between control and patients with VTE were significantly altered only for EDN T1370G polymorphism. The plasma EDN1 concentration was relatively higher in patients with VTE ( P = .0017) compared to healthy controls and showed an association with the EDN1 gene polymorphism in male Indian population. Logistic regression model analysis for EDN T1370G indicated a significant association between EDN G allele and occurrence of VTE. The EDN1 gene polymorphism may play a significant role in predicting individual's susceptibility toward VTE and its clinical progression.