Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic polymorphisms of the renin-angiotensin system (RAS) have been associated with coronary artery disease (CAD) but no relation between these polymorphisms and coronary atherosclerosis has yet been systematically evaluated. The CORGENE study is a cross-sectional study involving 463 Caucasians who underwent standardized coronary angiography for established or suspected CAD [156 patients with a previous myocardial infarction (MI), 307 without MI]. Four angiographic scores assessing the extent and severity of the coronary lesions were obtained from a double visual analysis of each angiogram, arbitration being achieved by a quantitative measurement. Three different genotypes were analyzed: the angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism, the Met to Thr change at position 235 of the angiotensinogen gene (AGT M235T) and the A to C transition at position 1166 of the angiotensin II type-1 receptor gene (AT1R A1166C). No significant association was observed between these polymorphisms and the clinical characteristics of MI and non-MI subjects. While most classical risk factors were positively correlated with the angiographic scores, no significant relationship could be established with the three genotypes (r ranging from -0.08 to 0.05). Only one significant correlation was observed: between the presence of the AGT 235T allele and the extent of the coronary lesions (r = -0.19, P = 0.04) in patients with low-risk status. These overall results are not in favor of a role of these RAS genetic polymorphisms in the development of coronary atherosclerosis.
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PMID:Genetic polymorphisms of the renin-angiotensin system and angiographic extent and severity of coronary artery disease: the CORGENE study. 900 97

Aim of this study is to carry out a genetic analysis of polymorphisms of the renin-angiotensin system in a genetically homogeneous population, in patients with and without myocardial infarction (AMI) expansion and to evaluate the influence of non genetic, mechanical factors. The study was conducted on 299 patients with first AMI. Ecocardiography studies were performed on all patients on day 1 and 3 from the onset of AMI and before discharge. Eighty-four patients were excluded because of inadequate quality of echocardiograms and 215 (163 males, 52 females) were admitted. Of these, 157 had no evidence of AMI expansion (EXP-) while 58 had expansion (EXP+). DNA was extracted by standard methods from blood samples. Age and gender had no influence on AMI expansion. Anterior infarction (p < 0.000001) and Q-wave infarction (p < 0.00002) were found more frequently in EXP+. Peak of creatine phosphokinase was higher in EXP+ than in EXP- (p < 0.00001). The percent of patients treated with thrombolysis or with hypertension and/or left ventricular hypertrophy was not significantly different in the two groups. AGT MT235 polymorphism of angiotensinogen gene, I/D polymorphism of ACE gene and AT1 A1166C of AT1 receptor of angiotensin II were not significantly different in two groups. Stratified analysis showed that in patients with anterior AMI (n = 87), with a higher risk of AMI expansion, there is a significant difference (p < 0.02) in ACE genotype between EXP- and EXP+. Odds ratio assuming the dominant effect of I allele (II+ ID < DD) was 3.35 (confidence interval 1.41-7.56) with increased risk of expansion. More extension studies are need to verify if these results can contribute to early identification of patients at higher risk and to optimize therapeutic approach.
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PMID:[Does a genetic predisposition for infarction expansion exist? Evaluation of genetic polymorphisms of the renin-angiotensin system]. 917 34

The groups of patients with myocardial infarction (MI) and hypertrophy of the left ventricle (HLV) (n = 45 and n = 53, respectively) and a sample of healthy individuals from the Moscow population (n = 60) were examined for T174M polymorphism of AGT gene (replacement of methionine for threonine at position 174 of the correspondent amino acid sequence). In MI patients the content of TT genotypes and T allele was significantly lower than in the control group (57.8% against 80% and 67.9 against 89.2%, respectively), whereas the proportion of M allele and TM heterozygotes was increased (32.1 against 10.8% and 37.8 against 18.3%, respectively). In patients with HLV, the proportion of TT genotype (64.2%) and T allele (77.4%) was also lower than in the control group, whereas the frequency of M allele was increased (22.6%). Our results suggest that the T174M polymorphism of AGT gene is associated with MI and HLV in the Moscow population.
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PMID:[Polymorphism of angiotensinogen T174M gene and cardiovascular diseases in the Moscow population]. 1054 20

Highly multiplexed genotyping methods are needed to support a comprehensive analysis of single nucleotide polymorphisms (SNPs) in coronary artery disease (CAD)-related genes. In this study we evaluated chip-based MALDI-TOF mass spectrometry for multiplexed genotyping of SNPs associated with CAD. Our analysis included 14 healthy Japanese individuals and 19 Japanese patients with myocardial infarction whose first attack occurred before age 50. We selected 29 candidate genes involved in 1) the renin-angiotensin system, 2) lipid metabolism, 3) cytokines and adhesion molecules, 4) growth factors, and 5) the coagulation-fibrinolysis system. Genotyping of candidate SNPs was performed by MALDI-TOF MS using a MassARRAY system, and 4-plex analysis was achieved at a maximum. All 39 SNPs determined by the fluorescent dye-terminator cycle sequencing method from four randomly selected patients were found to be in complete agreement with the results obtained from MassARRAY system. Significant differences were observed in the -1965delG of PAI1 (SERPINE1) with respect to allelic frequency, the G>A in the promoter region SNP in SM22 (TAGLN) for dominant genotype, and in two other SNPs (C>T in intron 1 of HGF, and -1965delG of PAI1) for recessive genotype. Three SNPs (803T>C of AGT, 677CT of MTHFR, 190T>C of ADRB3) showed weak differences in allelic frequency. MALDI-TOF-MS provided high performance with a multiplex assay design for analysis of CAD-related SNPs by increasing the throughput while maintaining a high level of accuracy.
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PMID:Highly multiplexed genotyping of coronary artery disease-associated SNPs using MALDI-TOF mass spectrometry. 1212 94

Angiotensinogen is an essential component of the renin-angiotensin system. ACE-inhibitors and beta-blockers both have a direct influence on this system. To investigate whether the association between use of ACE-inhibitors or beta-blockers and the risk of myocardial infarction (MI) or stroke is modified by the T-allele of the angiotensinogen M235T polymorphism. In this study, 4097 subjects with hypertension , aged 55 years and older, were included from the Rotterdam Study, a population-based prospective cohort study in The Netherlands, from July 1, 1991 onwards. Follow-up ended at the diagnosis date of MI, stroke, death, or the end of the study period (January 1, 2002). The drug-gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model with adjustments for each drug class as time-dependent covariates. The risk of MI was increased in current use of ACE-inhibitors with the MT or TT genotype compared to ACE-inhibitors with the MM genotype (Synergy Index (SI): 4.00; 95% CI: 1.32-12.11). A significant drug-gene interaction was not found on the risk of stroke (SI: 1.83; 95% CI: 0.95-3.54) in ACE-inhibitor users or between current use of beta-blockers and the AGT M235T polymorphism on the risk of MI or stroke. ACE-inhibitor users with at least one copy of the 235T-allele of the AGT gene might have an increased risk of MI and stroke.
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PMID:Angiotensinogen M235T polymorphism and the risk of myocardial infarction and stroke among hypertensive patients on ACE-inhibitors or beta-blockers. 1729 37

We assessed the prevalence and 3-month change in glucose tolerance status in consecutive non-ST-elevation myocardial infarction (NSTEMI; European Society of Cardiology 2007 definition) patients (N=49; mean (S.D.) age 65 (11) years) admitted to a coronary care unit, without known diabetes. These patients underwent an oral glucose tolerance test (OGTT) 36-hour (median, IQR: 18-72) after admission and at 3 months. Undiagnosed abnormal glucose tolerance (AGT: impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or new diabetes) was common (61% at admission and 41% at 3 months, p<0.05) and the majority (approximately 3/4) had IGT. Glucose tolerance status improved in a higher proportion of patients than it worsened (31% vs. 8%, p=0.04). At 3 months, fasting glucose was unchanged but 2-hour OGTT glucose was lower (mean (S.D.): 8.5 (2.7) mmol/L vs. 7.7 (2.7) mmol/L, p=0.004). 'Stress hyperglycaemia' could explain higher admission glucose levels and this raises the question about the optimal timing of OGTT in relation to myocardial infarction. Newly diagnosed diabetes was present in approximately 10% of patients and this was not reliably detected by fasting plasma glucose. In NSTEMI patients OGTT is the only reliable strategy to identify subjects with IGT and diabetes.
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PMID:Temporal change in glucose tolerance in non-ST-elevation myocardial infarction. 1884 19

The aim of the study was to describe the relationship of clinical outcome after percutaneous coronary intervention (PCI) with stenting and genetic polymorphisms (GP) which are known to relate to the incidence of in-stent restenosis and late thrombotic complications. The study included 190 patients with standardized clinical follow-up over 5 years, which were initially treated with PCI. We investigated clinical data, angiographic characteristics, 10 polymorphisms involved in neointimal hyperplasia and late thrombosis at 6 different levels and their relationship with the major adverse cardiac events (MACE). The long-term clinical outcome was defined by MACE: death, target vessel revascularization (PCI or coronary bypass grafting, CABG) and myocardial infarction. Angiotensin receptor type I (AGTR A1166C) and angiotensinogen (AGT MET235THR) GPs correlated with repeat revascularization and total MACE. Carriers of G allele for NOS3 A922G GP were shown to have a significantly lower repeat revascularization rate in comparison with the AA genotype, as did the T allele carriers in the NOS3 C690T GP analysis when compared to the CC genotype. The Asp genome carriers with the NOS3 GLU298ASP GP were also shown to have significantly less re-PCI in contrast to the Glu/Glu genotype. The study could document the protective influence of the 4G/5G GP for plasminogen inhibitor activator-1, which carried the lowest rate of re-PCI and total MACE during the follow-up. GPs for beta-1 G-protein subunit GNB3 C825T, fibrinogen FGB G455A and E-selectins Ser128Arg and Leu554Phe did not show statistical correlation with the clinical outcome. The results illustrate the potential use of genetic markers in defining patients with possibly worse clinical outcome after PCI, who may profit from more aggressive prevention of restenosis and late thrombotic complications.
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PMID:Relationship of genetic markers for atherosclerosis and long-term outcome after percutaneous coronary intervention with stenting. 2339 Aug 38

(1) Aims: Diabesity, defined as diabetes occurring in the context of obesity, is a serious health problem that is associated with an increased risk of premature heart attack, stroke, and death. To date, a key challenge has been to understand the molecular pathways that play significant roles in diabesity. In this study, we aimed to investigate the genetic links between diabetes and obesity in diabetic individuals and highlight the role(s) of shared genes in individuals with diabesity. (2) Methods: The interactions between the genes were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) tool after the compilation of obesity genes associated with type 1 diabetes (T1D), type 2 diabetes (T2D), and maturity-onset diabetes of the young (MODY). Cytoscape plugins were utilized for enrichment analysis. (3) Results: We identified 546 obesity genes that are associated with T1D, T2D, and MODY. The network backbone of the identified genes comprised 514 nodes and 4126 edges with an estimated clustering coefficient of 0.242. The Molecular Complex Detection (MCODE) generated three clusters with a score of 33.61, 16.788, and 6.783, each. The highest-scoring nodes of the clusters were AGT, FGB, and LDLR genes. The genes from cluster 1 were enriched in FOXO-mediated transcription of oxidative stress, renin secretion, and regulation of lipolysis in adipocytes. The cluster 2 genes enriched in Src homology 2 domain-containing (SHC)-related events triggered by IGF1R, regulation of lipolysis in adipocytes, and GRB2: SOS produce a link to mitogen-activated protein kinase (MAPK) signaling for integrins. The cluster 3 genes ere enriched in IGF1R signaling cascade and insulin signaling pathway. (4) Conclusion: This study presents a platform to discover potential targets for diabesity treatment and helps in understanding the molecular mechanism.
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PMID:Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity. 3311 59