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:2.6.1.44 (AGT)
770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Finding the genetic determinants of intermediate quantitative traits, such as serum creatinine and urea, might aid in finding the determinants of disease phenotypes, such as renal failure, that are, in part, defined according to threshold values imposed upon such traits. We evaluated the association between common variation in the gene encoding angiotensinogen, AGT, and the serum concentrations of creatinine and urea in non-diabetic Canadian Oji-Cree. We determined genotypes of the AGT codon 235 polymorphism among 502 non-diabetic Oji-Cree. We used multivariate analysis of variance to identify significant determinants of variation in serum concentrations of creatinine and urea and of systolic and diastolic blood pressure. We found significant associations between the AGT codon 235 genotype and serum concentrations of creatinine and urea (p = 0.017 and 0.049, respectively) and systolic blood pressure (p = 0.041). Compared with subjects with the other two genotypes, homozygotes for AGT T235/T235 had significantly lower serum concentrations of creatinine and urea and significantly higher mean systolic blood pressure. The findings suggest that the AGT T235 allele is a determinant of intermediate traits related to renal function in these aboriginal Canadians.
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PMID:Association between AGT codon 235 polymorphism and variation in serum concentrations of creatinine and urea in Canadian Oji-Cree. 1045 Aug 60

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

Urolithiasis is uncommon in adolescence and rare in early childhood. In pediatric populations, congenital urinary tract anomalies associated with stasis and infection, idiopathic urolithiasis (adolescents), and nephrocalcinosis (premature infants) account for the majority of urolithiasis patients. Inborn errors of metabolism, such as the primary hyperoxalurias, are rare causes of urolithiasis in childhood. We report six children (mean age at symptom onset 1.3 years; range 0.32-4.1 years) with moderate hyperoxaluria (mean 1.10 +/- 0.58 mmoL/1.73m2 per day; range 0.69-2.19 mmoL/1.73m2 per day). Urolithiasis was present in four. Stones from two children were comprised of calcium oxalate dihydrate. Calcium oxalate crystalluria was seen in two of the patients. Findings included a mean urine calcium concentration of 6.61 +/- 2.28 mg/kg per day, urine citrate of 925.5 +/- 291.29 mg/g of creatinine per day, and mean renal clearance of 99.83 +/- 23.27 mL/min. All children were born full term, none was receiving diuretics, and none had recurrent urinary tract infections. Secondary causes of hyperoxaluria, including dietary oxalate excess, pyridoxine deficiency, and malabsorption, were excluded. Urine glycolate and glycerate were normal in all patients. In one hyperoxaluric member of each sibship, hepatic alanine-glyoxylate aminotransferase and D-glycerate dehydrogenase/glyoxylate reductase activity were normal. The clinical and biochemical features of these children are unlike those in previously recognized hyperoxaluric states. Thus, our description of a separate hyperoxaluric entity, referred to as unclassified hyperoxaluria.
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PMID:Hyperoxaluria and urolithiasis in young children: an atypical presentation. 1060 14

Recent studies have shown that F2-isoprostane levels-a marker for lipid peroxidation-are increased in human renovascular hypertension but not in essential hypertension. Angiotensin II specifically stimulates F2-isoprostane production through activation of the AT1 receptor. The objective was to determine whether there is a relationship between the level of oxidative stress evaluated by measuring urinary F2-isoprostanes levels and polymorphisms of genes involved in the renine angiotensin aldosterone system (RAAS) regulation. The population studied included 100 subjects, 65 of whom were healthy normotensives; the other 35 were suffering from untreated, essential hypertension. The polymorphisms studied concern the genes encoding angiotensin I-converting enzyme (ACE/in16del/ins), angiotensin II receptor type I (AGTR1/A+39C[A+1166C] and AGTR1/A-153G), angiotensinogen (AGT/M235T), and aldosterone synthase (CYP11B2/T344C). Oxidative stress was evaluated by measuring urinary F2-isoprostanes levels. The characteristics of the population were as follows: men/women = 46/56; age = 50 +/- 10 years; BMI = 24 +/- 3 kg/m2; SBP = 131.7 +/- 17.2 mm Hg; DBP = 84.6 +/- 10.4 mm Hg. In univariate analysis, urinary F2-isoprostane levels were significantly lower in the presence of the G allele of AGTR1/A-153G (56 +/- 17 vs 76 +/- 39 pmol/mmol creatinine; P < 0.001, and P < 0.01 after Bonferroni correction for 10 tests). In multivariate analysis, taking into account BP, age, gender, BMI, plasma glucose, and total cholesterol, the G allele of AGTR1/A-153G is linked independently to urinary F2-isoprostanes level (P < 0.01). Our data suggest that F2-isoprostane level depends at least in part on the A-153G polymorphism of the angiotensin II AT1 receptor gene. The clinical and prognostic relevance of this polymorphism requires further investigation.
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PMID:F2-Isoprostane level is associated with the angiotensin II type 1 receptor -153A/G gene polymorphism. 1568 14

Recent studies have demonstrated some association between the renin-angiotensin system (RAS) activity and the development and progression of different entities as diabetes mellitus (DM) or chronic allograft nephropathy. To investigate these associations, we studied some gene polymorphisms of RAS in a group of renal transplant recipients. We retrospectively analyzed 42 patients who underwent a primary renal transplantation for 2 years. A subgroup of 23 patients (55%) was diagnosed with postransplant DM in accordance with American Diabetes Association 2001 criteria. We studied two RAS gene polymorphisms: the angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGTM235T). Genotyping was performed by DNA purification and amplification with a polymerase chain reaction technique. The distributions of genotypes were ACE DD, ID, II: 33%, 48%, 19%; and AGT TT, MT, MM: 15%, 45%, 40%, respectively. We observed a progressive loss in renal function measured by creatinine clearance (Cockroft) in D-allele carriers (DD+ID) between the first and the second transplantation year: 65.3 +/- 4.3 vs 59.8 +/- 4.6 mL/min (P = 0.02); that was not seen in II patients: 68.8 +/- 4.6 vs 68.4 +/- 4 mL/min (P = 0.87). Fifty percent of D-allele carriers developed DM vs 25% of non-D-allele carriers (P = 0.19). Eighty-three percent of homozygous patients for the AGT-TT allele developed DM vs 35% of non TT patients (P = 0.04). There were no significant differences regarding recipient demographic characteristics, type of donor, number and severity of acute rejections, and immunosuppressant treatment between the groups. In conclusion, ACE D-allele seems to be associated with a poorer kidney graft long-term outcome. ACE D and AGT T alleles may be implicated in glucose metabolism disorders after transplantation.
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PMID:Association of the genetic polymorphisms of the renin-angiotensin system with kidney graft long-term outcome: preliminary results. 1638 15

Heart failure (HF) is characterized by neurohormonal activation of the sympathetic nervous and renin-angiotensin systems. Genetic polymorphisms in these systems could alter the prognosis in HF. We hypothesized the genetic polymorphisms in the sympathetic nervous and renin-angiotensin systems are associated with adverse outcomes, defined as death or heart transplantation in patients with HF. A total of 227 patients with HF were enrolled from a tertiary care clinic and followed for outcomes for < or =4 years. Eight polymorphisms in 6 genes were genotyped: beta(1)-adrenergic receptor (ADRB1, S49G, R389G), beta(2)-adrenergic receptor (ADRB2, G16R, Q27E), alpha(2c)-adrenergic receptor (ADRA2C, insertion/deletion 322-325), angiotensinogen (AGT, M235T), angiotensin receptor type 1 (AGTR1, 1166A>C), and angiotensin-converting enzyme (ACE, insertion/deletion in intron 16). Most patients were treated according to consensus guidelines. Male gender (hazard ratio 2.24, 95% confidence interval 1.27 to 3.94), higher New York Heart Association functional class (hazard ratio 2.54, 95% confidence interval 1.84 to 3.52), and 2 copies of ADRB2 Arg16Gln27 haplotype (hazard ratio 1.91, 95% confidence interval 1.09 to 3.36) increased the risk of adverse outcomes. In contrast, a higher serum sodium level (hazard ratio 0.91, 95% confidence interval 0.86 to 0.97) and higher creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.98 to 0.99) decreased the risk of adverse outcomes. None of the other genotypes/haplotypes were associated with adverse outcomes. In conclusion, ADRB2 Arg16Gln27 haplotype may significantly increase the risk of adverse outcomes in patients with HF receiving contemporary HF pharmacotherapy.
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PMID:Relation of beta(2)-adrenoceptor haplotype to risk of death and heart transplantation in patients with heart failure. 1722 28

We recently reported that urinary excretion rates of angiotensinogen (U(AGT)) provide a specific index of intrarenal renin-angiotensin (ANG) system (RAS) status in ANG II-dependent hypertensive rats. When this is shown to be applicable to human subjects, a diagnostic test to identify those hypertensive patients most likely to respond to an RAS blockade could provide useful information to allow a mechanistic rationale for selection of an optimized approach to treatment of hypertensive patients. However, simple and accurate methods to measure human angiotensinogen (hAGT) are unavailable. For future studies of human subjects, we developed antibodies and a sensitive and specific quantification system for hAGT using a sandwich ELISA. We raised two antibodies against hAGT: a mouse monoclonal antibody and a rabbit polyclonal antibody. The standard curve of this ELISA exhibited a high linearity (0.31-20 ng/ml). The correlation coefficient was >0.99. Plasma angiotensinogen concentrations of healthy volunteers ranged from 28 to 71 microg/ml (n = 10). The ratio of U(AGT) to urinary creatinine concentration ranged from 5.0 to 30 microg/g (n = 7). Intra- and interassay coefficients of variation ranged from 4.4 to 5.5% and from 4.3 to 7.0%, respectively. This ELISA system had no cross-reactivity with major proteins in proteinuric urine samples, such as human albumin, immunoglobulin, or transferrin. Moreover, the cross-reactivity of the system with angiotensin peptides was also negligible. This hAGT ELISA will be a useful tool to investigate the relationship of U(AGT) and reactivity to antihypertensive drugs in hypertensive patients.
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PMID:Novel sandwich ELISA for human angiotensinogen. 1755 39

Non-invasive monitoring may be useful after kidney transplantation (KT), particularly for predicting acute rejection (AR). It is less clear whether chronic allograft nephropathy (CAN) is also associated with changes in urine cells. To identify non-invasive markers of allograft function in kidney transplant patients (KTP), mRNA levels of AGT, TGF-beta1, EGFR, IFN-gamma, TSP-1, and IL-10 in urine (Ur) samples were studied using QRT-PCR. Ninety-five KTP and 111 Ur samples were evaluated. Patients (Pts) were divided as, within six months (N = 31), and with more than six months post-KT (N = 64). KTP with more than six months post-KT were classified as KTP with stable kidney function (SKF) (N = 32), KTP with SKF (creatinine < 2 mg/dL) and proteinuria > 500 mg/24 h (N = 18), and KTP with biopsy proven CAN (N = 14). F-test was used to test for equality of variances between groups. IL-10 mRNA was decreased in Ur samples from KTP with less than six months post-KT (P = 0.005). For KTR groups with more than six months post-KT, AGT and EGFR mRNA were statistically different among KTP with SKF, KTP with SKF and proteinuria, and CAN Pts (P = 0.003, and P = 0.01), with KTP with SKF having higher mean expression. TSP-1 mRNA levels also were significantly different among these three groups (P = 0.04), with higher expression observed in CAN Pts. Using the random forest algorithm, AGT, EGFR, and TGF-beta1 were identified as predictors of CAN, SKF, SKF with proteinuria. A characteristic pattern of mRNA levels in the different KTP groups was observed indicating that the mRNA levels in Ur cells might reflect allograft function.
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PMID:Evaluation of gene panel mRNAs in urine samples of kidney transplant recipients as a non-invasive tool of graft function. 1762 13

Primary hyperoxaluria (PH) is a rare autosomal recessive disease caused by the functional defect of alanine-glyoxylate aminotransferase (AGT) enzyme in the liver and it is characterized by the deposition of diffuse calcium oxalate crystals. A 38-year-old male patient presented with history of recurrent nephrolithiasis and has received chronic hemodialysis treatment for 2 years. Cadaveric renal transplantation was applied to the case. The patient was reoperated on postoperative day 13 because of the collection surrounding the urethra. During this operation, kidney biopsy was made due to late decrease in creatinine levels. Deposition of diffuse oxalate crystal was detected in allograft kidney biopsy, whereas in the 0-hour biopsy there were no oxalate crystals. Oxalate level was found to be high in a 24-hour urine specimen (118 mg/L, normal level: 7-44 mg/L). The patient was identified with primary hyperoxaluria and followed up in terms of systemic oxalate deposition as well as allograft kidney. In the kidney biopsy taken after 18 months, we detected that oxalate crystals almost entirely disappeared. In our case, bilateral preretinal, intraretinal, and intravascular diffuse oxalate crystals were detected, and argon laser photocoagulation treatments were needed for choroidal and retinal neovascularization. Repeated ophthalmic examinations showed the regressive nature of oxalate depositions. In the 18th month, fundus examination and fluorescein angiography revealed that oxalate crystals were significantly regressed. To increase the quality of life and slow down the systemic effects of oxalosis, kidney-only transplantation is beneficial.
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PMID:Regressive course of oxalate deposition in primary hyperoxaluria after kidney transplantation. 2086 24

Renal stone disease may ensue from either derangements of urine biochemistries or anatomic abnormalities of kidneys and urinary tract. Genetic, environmental and dietary factors may also cooperate in the pathophysiology of nephrolithiasis. An adequate metabolic evaluation should focus on the urinary excretion of promoters and inhibitors of stone formation as well as on the occurrence of systemic diseases potentially related to secondary nephrolithiasis (i.e., endocrine disturbances, malabsorption, bone diseases). Moreover, metabolic investigations should provide reliable information on patient's dietary habits, guide towards the best therapeutic approach and enable the physician to verify patient's compliance to prescribed therapies.AN EXTENSIVE METABOLIC EVALUATION IS RECOMMENDED IN PATIENTS WITH ACTIVE STONE DISEASE (NAMELY, AT LEAST ONE NEW STONE WITHIN THE LAST TWO YEARS), OR IN THOSE HAVING HAD A SINGLE STONE EPISODE OCCURRED IN PECULIAR CONDITIONS: familial history of disease, childhood, menopause, pregnancy, systemic diseases. Simplified protocols may be adequate in non-active nephrolithiasis or in patients with single stone and no relevant risk factors.In our Stone Centre, a so-called "first level screening" is performed by routine, in order to assess urinary supersaturation with stone forming salts and evaluate the excretion of dietary-related metabolites in urine. Relative blood and urine determinations are reported below.IN VENOUS BLOOD: urea, creatinine, uric acid, Na, K, total and ionised Ca, Mg, P, Cl, alkaline phosphatase, gas analysis. In 24-hr urine samples: urea, creatinine, uric acid, Na, K, Ca, Mg, P, Cl, oxalate, inorganic sulphate, citrate, pH, ammonia and titratable acidity. IN FASTING URINE SAMPLES: Ca, citrate, creatinine, hydroxyproline, Brand's test for cistinuria, urine sediment, urine culture. If the first-level evaluation suggested an abnormal bone turnover, then further determinations are warranted, namely, calciotropic hormones (blood Vitamin D and PTH), markers of bone resorption (urine pyridinium crosslinks, serum crosslaps) and formation (serum osteocalcin) bone mineral density.EVENTUALLY, MORE SOPHISTICATED INVESTIGATIONS ARE REQUIRED TO IMPROVE THE DIAGNOSIS OF PECULIAR DISEASES: serum oxalate and glycolate, urine glycolate and L-glycerate, hepatic AGT activity (primary hyperoxalurias); genetic tests (hereditary nephrolithiasis); acidification tests (renal tubular acidosis).
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PMID:Biochemical evaluation in renal stone disease. 2246 Sep 94


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