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)

We previously found an association between blood pressure and genetic variation of angiotensinogen in Canadian Hutterites. We hypothesized that variation in other candidate genes would also be associated with variation in blood pressure. We included genotypes of 12 candidate genes, along with clinical features and biochemical variables as covariates in an association analysis. We found that sex and body mass were significantly associated with variation in both systolic and diastolic blood pressures. We found that genotypes of APOB codon 4154 and AGT codon 174 were significantly associated with variation in systolic blood pressure. We found that genotypes of APOB codon 4154, AGT codon 174, and F7 codon 353 were significantly associated with variation in diastolic blood pressure. We found a significant association between age and variation in systolic but not diastolic blood pressure. We found a significant association between plasma apo B concentration and variation in diastolic but not systolic blood pressure. The association of genomic variation with resting blood pressure is consistent with the existence of important structural elements within or proximal to some genes in lipoprotein metabolism, the renin-angiotensin system, and the coagulation cascade. The association between plasma apo B concentration and diastolic blood pressure suggests that these traits may share some determinants.
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PMID:Genetic and biochemical factors associated with variation in blood pressure in a genetic isolate. 856 57

1. The association of different patterns of left ventricular hypertrophy and diastolic dysfunction with angiotensin converting enzyme (ACE) genotypes or angiotensinogen dinucleotide repeat alleles were studied in human subjects. 2. Three abnormal patterns of hypertrophy (remodelled, eccentric and concentric) were associated with a history of hypertension. The presence of remodelled or concentric hypertrophy was associated with diastolic dysfunction. 3. There was no difference between the frequencies of the ACE genotypes in normotensive and hypertensive subjects, in subjects with normal ventricles and those with different patterns of left ventricular hypertrophy, nor in subjects with normal and abnormal diastolic function. Similarly, there was no difference between the relative frequencies of AGT alleles in the same clinical subgroups. 4. We conclude that in this population of hospital patients, variants of the ACE and AGT genes do not contribute to the presence of different patterns of hypertrophy or to diastolic dysfunction.
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PMID:Angiotensin-converting enzyme and angiotensinogen genes in patterns of left ventricular hypertrophy and in diastolic dysfunction. 858 95

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

A close relationship between obesity and hypertension has been recognized, and plasma angiotensinogen concentrations (p-AGT) have been reported to correlate with blood pressure (BP). However, little is known about AGT in obese patients with hypertension. To define the role of AGT in obese hypertension, we measured p-AGT in obese patients. The subjects were 42 obese patients diagnosed on the basis of a body mass index (BMI) of more than 25 kg/m2, and 21 sex- and age-matched nonobese patients, whose BMI was less than 25 kg/m2. The hypertensive patients had not previously received antihypertensive drugs. P-AGT (P < .05) and mean BP (P < .0001) was increased in the obese patients as compared with the nonobese patients. Positive correlations were observed between BMI and p-AGT, mean BP and p-AGT, and BMI and mean BP (all P < .05). However, after adjustment for blood pressure, p-AGT was not different between groups, and after adjustment a positive correlation remained only between BMI and mean BP. These results suggested the possible involvement of increased p-AGT in hypertension in obese patients, although this may be a secondary change to hypertension or obesity.
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PMID:Plasma angiotensinogen concentrations in obese patients. 919 8

Recently, an allelic variant of the angiotensinogen gene (AGT 235T) has been associated with increased risk of hypertension. However, this finding has not been confirmed by all investigators. A meta-analysis was performed to examine the association between the AGT 235T-allele and hypertension in whites and to identify potential reasons for the controversial results. All relevant articles published between 1992 and 1996 were identified through multiple sources. The studies were methodologically appraised, and the frequency of the AGT 235T-allele was extracted. The 235T-allele frequency was pooled using the common odds ratio (OR) estimator by Mantel-Haenszel. Homogeneity was assessed using the Breslow-Day test. Together these studies present data on 5493 patients. The AGT 235T-allele was significantly associated with hypertension (OR: 1.20; 95% [CI]: 1.11 to 1.29; P<.0001). This association increased in studies with positive family history (OR: 1.42; 95% CI: 1.25 to 1.61, P<.0001), recruitment of cases from referral centers (OR: 1.39; 95% CI: 1.20 to 1.62, P<.0001), and more severe hypertension (OR: 1.34; 95% CI: 1.22 to 1.47, P<.0001). However, the presence of methodological problems in all studies gives rise to serious concerns regarding bias and confounding. Despite a statistically significant, albeit weak, association between the AGT 235T variant and hypertension that has been confirmed through sensitivity analysis, this finding has to be interpreted with caution, as the methodological weaknesses of the individual studies are likely to have biased the outcome of the meta-analysis. Clearly, more rigorous methods need to be applied in association studies on the genetics of human hypertension.
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PMID:Association between the angiotensinogen 235T-variant and essential hypertension in whites: a systematic review and methodological appraisal. 940 49

We previously reported significant associations between variation in the AGT gene at codon 235 and both systolic pressure and hypertension in Canadian Oji-Cree. Recently, Inoue et al suggested that the AGT T235 variant was not causative, but was rather in linkage disequilibrium with a variant in the AGT promoter, namely -6A, that was associated with increased in vitro expression of angiotensinogen and was thus a strong candidate to be the functional basis of the previously observed associations. We genotyped 518 adult Oji-Cree for the AGT promoter polymorphism and tested for its association with blood pressure and hypertension. We found that the frequency of the -6A variant was 0.85 in the Oji-Cree, which is much higher than the frequency observed in other human samples. We also found strong linkage disequilibrium between the AGT -6A and T235 variants. However, genetic variation of the AGT promoter was only marginally associated with variation in systolic pressure, with a trend to significantly higher systolic pressure seen in AGT -6A/A homozygotes than in subjects with other genotypes. In addition, genetic variation of the AGT promoter tended to be associated with a diagnosis of hypertension. Despite the very high prevalence of -6A, our native sample was essentially normotensive. Our findings are consistent with a marginally deleterious effect of the AGT -6A allele on blood pressure, but linkage disequilibrium with another causative variant cannot be ruled out in this sample of aboriginal Canadians.
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PMID:-6A promoter variant of angiotensinogen and blood pressure variation in Canadian Oji-Cree. 960 96

Transgenic mice containing the human angiotensinogen (HAGT) gene were utilized to determine the developmental regulation of HAGT expression. RNase protection assay on total RNA obtained from whole transgenic fetuses revealed that HAGT expression was first detected at embryonic day 8.5 (E8.5) and was abundant from E9.5 onward. The earliest expression of the HAGT transgene appeared to precede the earliest expression of the endogenous mouse AGT gene by 1-2 days. Northern blot analysis revealed moderate levels of HAGT mRNA in liver and kidney and low levels of HAGT mRNA in heart and brain from E16.5 (day 16.5 of gestation) onward. HAGT mRNA in liver, although abundant during late gestation and in 2-wk-old and adult mice, decreased transiently around birth. In situ hybridization performed on sections from whole fetuses revealed that HAGT mRNA was restricted to the developing liver and heart between E9.5 and E11.5 but became more widespread to include the developing aorta, brain, subcutaneous tissues, and vertebra at E13.5. In situ hybridization analysis on fetal kidneys from late gestation, newborn, and 2-wk-old mice demonstrated a progressive restriction of HAGT mRNA to developing cortical proximal tubular cells. These data illustrate the developmental tissue-specific regulation of HAGT expression and demonstrate that sequences present in the transgene can confer an appropriate developmental expression profile.
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PMID:Developmental expression of human angiotensinogen in transgenic mice. 961 31

According to the "thrifty-genotype" hypothesis proposed by Neel, diseases of civilization such as non-insulin-dependent diabetes mellitus and hypertension result from a discordance between certain features of our present-day environment and our genetic make-up which evolved to fit the life of Paleolithic humans. This concept implies that while "affected" individuals harbor the "original" ancestral version of the relevant genes, healthy or "unaffected" individuals have picked up recent mutations leading to a "loss of thriftiness" of these genes. Support for this concept now comes from recent studies of the angiotensinogen gene, where an ancestral variant of the gene (AGT 235T), also present in primates, has now been associated with hypertension whereas a neomorphic variant (AGT 235M) apparently reduces the risk of high blood pressure. The implications of these findings for our understanding and approach to the study of complex genetic diseases is discussed.
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PMID:The thrifty-genotype hypothesis and its implications for the study of complex genetic disorders in man. 969 33

Gene coding for the main components of the renin-angiotensin system have been characterized and localized: angiotensinogen (AGT, chromosome 1q42), renin (REN, chromosome 1), angiotensin I-converting enzyme (ACE, chromosome 17), angiotensin II receptors (AT1R, chromosome 3 and AT2R, chromosome X). A positive linkage and association have been found between AGT and essential hypertension. M235T is also associated with plasma AGT concentration. In vitro studies suggest that a polymorphism (G-6A) which is in complete linkage disequilibrium with M235T and which is located in the promoter close to the start of transcription might explain this association with high blood pressure. The ACE I/D polymorphism explains about 30 to 40 per cent of the variance of plasma ACE levels. Although the ACE gene itself does not seem to play a role in blood pressure level, the corresponding chromosomal region has been linked to blood pressure in both spontaneously hypertensive rats and humans. In tissues, an increased ACE activity may explain the association between the ACE I/D polymorphism and coronary heart disease, left ventricular hypertrophy, neointimal proliferation in vessels and progression of diabetic and IgA nephropathy.
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PMID:[Genetic polymorphisms in the renin-angiotensin system]. 977 26


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