Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin-angiotensin system (RAS) is involved in the pathogenesis of essential hypertension. In the present study we examined the genotype frequencies of the insertion/deletion polymorphisms of the ACE gene and the M235T polymorphism of the Angiotensinogen (Agt) gene in patients with essential hypertension in comparison with normotensive subjects. In hypertensive patients functional effects of blood pressure response to ACE inhibition were investigated. A total of 121 patients with essential hypertension (group 1) and 125 normotensive control subjects (group 2) were included in this study. All patients were genotyped by polymerase chain reactions (PCR) for the insertion/deletion (I/D) polymorphism of the ACE gene and the M235T polymorphism of the Agt gene. To analyze possible functional impacts on blood pressure regulation 50 mg of captopril was administered to hypertensive patients. No significant association of essential hypertension with polymorphisms of the Agt and ACE gene was found. The ACE serum levels in patients with the DD-genotype of the ACE I/D polymorphism were higher than in patients with the II-genotype (P < .01). In patients with the ID-genotype the ACE serum levels were in-between. A captopril test was performed in hypertensive patients. The patients were further divided into subgroups according to the diastolic and systolic blood pressure response. Group 1a consisted of patients with a diastolic blood pressure drop of > 5 mm Hg and group 1b with < or =5 mm Hg. Group 1c consisted of patients with a systolic blood pressure drop of > 10 mm Hg and group 1d with < or =10 mm Hg. Twice as many patients with the DD genotype of the ACE gene were found in group 1a compared to group 1b (chi(2) = 5.673; P = .017). No association of systolic blood pressure change to the investigated polymorphisms was found. Our results do not support the hypothesis that the investigated polymorphisms contribute to essential hypertension. Furthermore, no major impact of these polymorphisms on blood pressure response to captopril were detected. We conclude that the investigated genotypes have no influence on blood pressure level and homeostasis.
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PMID:Contribution of angiotensin I converting enzyme gene polymorphism and angiotensinogen gene polymorphism to blood pressure regulation in essential hypertension. 952 45

In a hospital cohort study, we examined whether or not ACE (Angiotensin-I converting enzyme) and AGT (Angiotensinogen) gene polymorphisms were associated with the development of nephropathy in long-term Japanese insulin-dependent diabetes mellitus (IDDM) patients with or without proliferative retinopathy, and whether or not the polymorphisms were associated with an arteriosclerotic family history in first degree relatives of the patients. A total of 201 patients with IDDM for more than 10 years and 159 patients with IDDM for more than 15 years were randomly selected in our hospital. All patients received uniform diabetes management and were divided into three groups, no nephropathy, incipient nephropathy and clinical nephropathy groups. There were no differences in clinical characteristics excluding urinary albumin to creatinine ratio and systolic blood pressure between the three groups. ACE I/D polymorphism was related to plasma ACE activity, but there were no associations between ACE I/D polymorphism and the development of diabetic nephropathy, nor was renal deterioration observed in patients with proliferative retinopathy even in those with a history of diabetes for more than 15 years. The AGT polymorphism did not have an additive effect on the association between ACE polymorphism and the development of diabetic nephropathy in patients with or without retinopathy. Development of diabetic nephropathy in the patients with or without proliferative retinopathy did not result in ACE or AGT polymorphisms. On the other hand, the ACE DD genotype was associated with a family history of ischemic heart disease in first degree relatives (X2 score = 9.04, P < 0.05). ACE and AGT gene polymorphisms may not play a role in the protective or accelerative effect against the development of diabetic nephropathy in the patients with or without proliferative retinopathy, but ACE gene polymorphism might be related to an arteriosclerotic family history in Japanese IDDM patients.
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PMID:Genetic polymorphism of renin-angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus. 1049 84

Angiotensinogen (AGT) and angiotensin I-converting enzyme (ACE) are heritable traits, but whether the environmental context influences heritability has not been examined. Known genetic factors explain only a portion of variation in AGT and ACE, and levels of both proteins are influenced by the environment. The African diaspora provides an opportunity to compare these traits in genetically related populations in contrasting environments. As part of a study of the genetics of hypertension, we examined families that included 1449 Nigerians and 1147 African Americans. Body mass index (weight [kg]/height [m](2)) was 21 kg/m(2) in Nigeria and 29 kg/m(2) in the United States, which is consistent with a large environmental contrast. AGT was considerably higher among African Americans (1919 versus 1396, P<0.01), whereas ACE was higher in Nigerians (630 versus 517, P<0.01). A household effect was observed among the Nigerian families (spouse correlations 0.30 for AGT, 0.18 for ACE), and correlations among first-degree relatives were large (0.42 to 0. 51 and 0.36 to 0.38 for AGT and ACE, respectively). Among African Americans, the familial aggregations of AGT and ACE were very limited, and the familial correlation for AGT was not different from zero. Heritability was 77% for AGT and 67% for ACE in Nigeria and 18% for AGT and ACE in the United States. The familial patterns of body mass index and blood pressure were similar among both family sets. In conclusion, less familial aggregation was observed for AGT and ACE in the United States than in Nigeria, most likely reflecting a greater random individual environmental effect on these traits. Variation in heritability of traits could influence the power of epidemiological studies to identify genetic effects.
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PMID:Heritability of angiotensin-converting enzyme and angiotensinogen: A comparison of US blacks and Nigerians. 1081 78

Essential Hypertension (EH) is a multifactorial and polygenic syndrome with a high impact in public health. Recently, rare mendelian forms of hypertension such as glucocorticoid-remediable aldosteronism (GRA), apparent mineralocorticoid excess (AME) and Liddle Syndrome caused by single gene mutations have been identified in which the mechanism is an increased sodium retention. Therefore, it is tempting to speculate that the most common forms of EH may be due to diverse highly prevalent molecular variants of susceptibility genes with low penetrance that are involved in arterial blood pressure (ABP) and electrolytic balance. Although a number of candidate genes such as NO synthases, ANP, ion transporters, adducins, LDL receptor, etc. can participate, renin-angiotensin system components are the most extensively studied. Although not associated with EH, the ACE D allele seems to confer a high risk of CHD or LVH. Angiotensinogen 235T and 174M variants are more likely associated with EH and positively correlate with clinical or ambulatory ABP in adolescents or adults. Individuals who carry these angiotensinogen alleles would be at 1.4 higher risk of suffering EH than homozygotes for M235 or T174 alleles. Associations of AT1 receptor variants with EH remain to be definitively defined. In conclusion, the characterization of the genetic background, although difficult at the present time, may have clear benefits in terms of defining a more rational therapy and prevention in individuals at risk. Even though this aim seems difficult to achieve since more than 150 candidate genes have been postulated as the cause of EH, with 6 to 10 SNPs in each of them, new technologies such as DNA micro-arrays will provide us with the opportunity to analyse the total genetic risk in each subject.
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PMID:[Molecular genetics of essential hypertension. Susceptibility and resistance genes]. 1083 1

Recent advances in genetic determination of human essential hypertension (EHT) are discussed by reviewing the candidate genes. Candidate genes have been selected based on genetic information from classical linkage analysis (affected sib-pair analysis) or mendelian hypertension (autosomal dominant inheritance of hypertension). Most of these genes are, directly or indirectly, coupled to salt handling of the kidney, being included in the renin-angiotensin system (RAS), steroid-hormone metabolism, and renal sodium transporters. Angiotensinogen (AGT) gene in RAS was first described as a strong candidate associated with the onset of hypertension, since sib-pair linkage analysis has demonstrated the trait loci for hypertension which includes the coding region for AGT. M235T polymorphism of AGT has been studied extensively in many populations including Japanese, and the results suggest a weak, but significant linkage with hypertension. The presence (insertion [I]) or absence (deletion [D]) of 287bp in intron 16 of angiotensin converting enzyme gene has also been examined in RAS, and the results suggest D polymorphism as a risk factor for hypertension in men. Other components in RAS, such as renin, angiotensinogen II type I receptor, or kallikrein have also been studied, but the available information is still incomplete. Genetic investigations of mendelian hypertension has identified the genetic mechanisms for glucocorticoid remediable aldosteronism, apparent mineral corticoid excess, and Liddle's syndrome as chimeric gene duplications of CYP11B1 (aldosterone synthase gene) and CYP11B2 (11beta-hydroxylase gene), mutations in the gene of 11beta-hydroxysteroid dehydrogenase type 2 that catalyzes the conversion of cortisol to cortisone, and mutations in beta or gamma subunit of epithelial sodium channel (ENaC), respectively. Subsequently, genetic variants of CYP11B2 and beta or gamma subunit of ENaC have been found, suggesting the -344C polymorphism of CYP11B2, 594S variant of betaENaC, and two rare variants of gammaENaC as risk factors for EHT. In spite of the extensive research, haplotypes in individual populations remain to be elucidcated in most candidate genes. Even casual conclusions of possible linkage with EHT need to be further examined with better determinations of phenotypes, such as ambulatory and home blood pressure monitoring or identification of onset of hypertension in cohort studies.
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PMID:Genetic determination of human essential hypertension. 1112 65

To evaluate the expression of the renin-angiotensin system (RAS) genes in visceral (VAT) and subcutaneous adipose tissue (SAT) in normotensive subjects with different body mass index (BMI). Adipose tissue was obtained from 22 normotensive (12 normal weight and 10 overweight) patients during surgery for colecystectomy. Angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), angiotensin converting enzyme (ACE) mRNA, and protein levels were measured by reverse transcriptase-polymerase chain reaction and Western blot analysis, respectively. The AGT mRNA and AT1 receptor mRNA levels were significantly higher in VAT than in SAT; AGT mRNA levels were higher, although not significantly, in overweight subjects in both SAT and VAT. There was no significant difference in ACE gene expression in the two tissues, and no expression of angiotensin II receptor type 2 (AT2). Finally, we failed to find mRNA for the renin gene in adipose tissue. The presence of AGT and ATI receptor in SAT and VAT was confirmed by Western blot analysis. Our study demonstrates the presence--and different levels of expression--of the various components of the RAS system (AGT, ATI, and ACE) in human SAT and VAT, and highlights the different role and regulation of the system in the two tissues. Its high expression in VAT suggests that its regulation and function are involved in all conditions where visceral adiposity is present.
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PMID:Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects. 1202 38

The renin-angiotensin system (RAS) is involved in the maintenance of fluid homeostasis in vertebrates. Production of the precursor protein, angiotensinogen, is regulated by other components within the RAS. Angiotensin II (Ang II) stimulates the production and secretion of angiotensinogen in many mammalian models. However, the existence of a similar positive feedback mechanism for angiotensinogen has not been demonstrated for any non-mammalian species. In the present study, we have cloned the angiotensinogen for silver sea bream (Sparus sarba) and investigated the role of Ang II on angiotensinogen expression. The nucleotide sequence of angiotensinogen for S. sarba only exhibits a fair resemblance to other fish angiotensinogens and shows 76.6% similarity to that of Takifugu rubripes and 57.2% similarity to that of Danio rerio. Angiotensinogen transcripts have been identified in the brain, liver, kidney, and various parts of the intestine of sea bream, an observation, which probably implies the presence of a local RAS at the tissue level. The liver is probably the major source of angiotensinogen, as it exhibits the highest angiotensinogen transcript abundance among different tissues. Differential angiotensinogen expression was found among different regions of the intestine where the pyloric caeca exhibits the highest expression. Putative Ang I is identified at the N-terminal of the deduced protein with a novel sequence [Asn1, Ile5, His9]-Ang I. Hepatic angiotensinogen expression in sea bream adapted to different salinities remained constant and this is probably due to desensitization of the angiotensin receptors by angiotensin. A positive feedback mechanism of angiotensinogen by Ang II has been demonstrated as exogenous Ang II increased the amount of angiotensinogen transcript in isolated hepatocytes in vitro. Blockade of endogenous RAS by the angiotensin converting enzyme (ACE) inhibitor, captopril, significantly lowered the hepatic expression of angiotensinogen in vivo. The effect of Ang II stimulation on angiotensinogen expression is more potent in fish than that in mammals. These data suggest that the positive feedback mechanism of angiotensinogen by Ang II has already evolved in teleosts and such mechanism may be involved in the maintenance of angiotensinogen secretion under resting and hypertensive conditions.
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PMID:Positive feedback of hepatic angiotensinogen expression in silver sea bream (Sparus sarba). 1702 45

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

In contrast to the current belief that angiotensin II (Ang II) interacts with the sympathetic nervous system only as a circulating hormone, we document here the existence of endogenous Ang II in the neurons of rat and human sympathetic coeliac ganglia and their angiotensinergic innervation with mesenteric resistance blood vessels. Angiotensinogen - and angiotensin converting enzyme-mRNA were detected by using quantitative real time polymerase chain reaction in total RNA extracts of rat coeliac ganglia, while renin mRNA was untraceable. Cathepsin D, a protease responsible for cleavage beneath other substrates also angiotensinogen to angiotensin I, was successfully detected in rat coeliac ganglia indicating the possibility of existence of alternative pathways. Angiotensinogen mRNA was also detected by in situ hybridization in the cytoplasm of neurons of rat coeliac ganglia. Immunoreactivity for Ang II was demonstrated in rat and human coeliac ganglia as well as with mesenteric resistance blood vessels. By using confocal laser scanning microscopy we were able to demonstrate the presence of angiotensinergic synapses en passant along side of vascular smooth muscle cells. Our findings indicate that Ang II is synthesized inside the neurons of sympathetic coeliac ganglia and may act as an endogenous neurotransmitter locally with the mesenteric resistance blood vessels.
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PMID:Angiotensinergic neurons in sympathetic coeliac ganglia innervating rat and human mesenteric resistance blood vessels. 1830 7

Substantial evidence suggests that the intrarenal renin-angiotensin system (RAS) plays a role in the pathogenesis of diabetic nephropathy. Although the glomerular RAS is activated in the streptozotocin (STZ)-diabetic rat, the status of the glomerular RAS in the Zucker diabetic fatty (ZDF) rat, which is a commonly used genetic model of diabetes, is not known. Angiotensinogen (AGT), angiotensin II (Ang II), angiotensin converting enzyme (ACE), and angiotensin converting enzyme 2 (ACE2) were measured in glomeruli isolated from 4-week-old STZ-diabetic rats and 32-week-old ZDF rats. Glomerular injury was evaluated by histopathologic methods. Both STZ-diabetic and ZDF rats exhibited marked hyperglycemia and renal hypertrophy, but only ZDF rats demonstrated proteinuria and glomerulosclerosis. Glomerular AGT and Ang II levels were increased significantly in STZ-diabetic compared with nondiabetic control rats, accompanied by a reduction in ACE2 activity. In contrast, glomerular AGT, Ang II, and ACE2 were similar in ZDF rats and lean controls. ACE levels were not affected by diabetes in either diabetic model. In conclusion, the glomerular RAS is activated in the STZ diabetic rat but not in the ZDF rat despite a similar degree of hyperglycemia. The mechanism of nephropathy in the ZDF rat may involve factors other than hyperglycemia and RAS activation, such as hypertension and hyperlipidemia.
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PMID:Glomerular renin angiotensin system in streptozotocin diabetic and Zucker diabetic fatty rats. 1835 68


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