Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An angiotensin II antagonist, sarcosine-1, threonine-8 angiotensin II ( [Sar1, Thr8] A II), was infused preoperatively in 14 patients with renal artery stenosis. Postoperative graft patency was documented by renal flow scan in 13 patients. One of these required antihypertensive therapy immediately after surgery, while the other 12 had a significant BP reduction in the first postoperative week (141 +/- 3.7 to 110 +/- 1.6 mm Hg). With longer follow-up, six patients remained normotensive (group 1), while the other six had "residual hypertension" (group 2). There was no significant difference between the two groups as regards age, preoperative BP level, plasma renin activity, blood volume, or response to [Sar1, Thr8] A II. In contrast, clinical signs were most helpful in predicting response to surgery. "Cured" patients had shorter duration of hypertension (less than one year) than patients with residual hypertension, and less impairment of renal excretory function; three patients in group 2 but none in group 1 had a history of malignant hypertension. The decision to operate remains a multifactorial evaluation and cannot be based on results of any single test alone.
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PMID:Predictive value of angiotensin II antagonists in renovascular hypertension. 633 2

A lot of over 60 atherosclerotics with clinical manifestations of senile depressive illness was studied comparatively with a lot of subjects of the same age with essential arterial hypertension (EAH). As concerns the behaviour of the catecholamine content in CSF and blood, the total catecholamines are approxiately equal in the two lots, but with a clear difference of the catecholamine fractions. The CSF catecholamines behaviour in old atherosclerotics is characterized by the presence of increased values of noradrenaline (NA) and of adrenaline (A), with increased statistical significance, but without modifications of the adrenaline percentage (A %) from the total catecholamines, comparatively to the values found in normal subjects. The serotonin (5-HT) content of the CSF in men with atherosclerotic senile depressive illness was lower even than in subjects with coronary atherosclerosis. In atherosclerosis protides modifications precede the histologic changes. In CSF, GLU, ALA, TYR increase in old subjects. In blood, GLU, ALA, TYR, HIS, LEU, SER increase in the same subjects. ARG decreases with age. THR is higher in men than in women. In the urine of all the men as well as of all the women of more than 60 years, GLN and ALA have increased values. LYS increases with age. GLN and ARG are higher in men than in women.
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PMID:Pattern of the cerebrospinal fluid (CSF) and blood biogenic amines and of the CSF, blood and urine amino acids as pathogenetic ground of the senile depressive illness. 677 91

Administration of an angiotensin II antagonist, (sarcosine-1, threonine-8) angiotensin II, was used to diagnose renovascular hypertension in 22 patients before renal revascularization or nephrectomy. Positive and negative responses to infusion occurred in 12 and 10 patients, respectively. Postoperatively, hypertension was cured in 13 patients, improved in 6 and unchanged in 3. The over-all accuracy of the infusion test in predicting the outcome of surgical therapy was 59 per cent, the false positive rate was 8.3 per cent and the false negative rate was 80 per cent. A similar high incidence of false negative results has been observed with differential renal vein plasma renin assays. The most accurate prediction of the blood pressure response to surgical therapy is obtained by considering multiple factors rather than a single test.
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PMID:Predictive value of angiotensin II blockade with (sarcosine-1, threonine-8) angiotensin II in renovascular hypertension. 682 87

A higher frequency of a variant of the angiotensinogen gene characterized by a transition in exon 2 causing a replacement of methionine by threonine (M235T) has recently been found in hypertensive individuals, but not all authors were able to confirm this observation. We examined (i) 219 patients with primary hypertension, (ii) 92 normotensive controls (spouses), and (iii) a sample of the general population (blood donors, n = 139). Analysis of genomic DNA was performed by PCR amplification and alleles were separated on agarose gels. In the general population and in normotensive spouses the respective frequencies of the T and M alleles were: general population: M = 0.6, T = 0.4; normotensive spouses: M = 0.59, T = 0.41. A significantly higher frequency of the 235T allele was found in hypertensive individuals with a family history of hypertension and an onset of hypertension before 50 years of age (spouses: 0.41 versus HT with age of onset < or = 50 years and family history of HT: 0.56; P = 0.01 by chi 2). In conclusion, the present study confirms the observation of a higher frequency of the 235T allele of the angiotensinogen gene in hypertension and identifies individuals with family history and early onset of hypertension as individuals at risk.
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PMID:Association of M235T variant of the angiotensinogen gene with familial hypertension of early onset. 747 15

As part of the multicenter project entitled "Pathobiological Determinants of Atherosclerosis in Youth (PDAY)," we are testing polymorphisms in candidate genes of atherosclerosis and hypertension for associations with arterial lesions in autopsied young persons. In this study, we used temperature gradient gel electrophoresis (TGGE) to type the Met235-->Thr polymorphism in exon 2 of the angiotensinogen gene (AGT) that is associated with essential hypertension in some human populations. In addition to Met235-->Thr, we detected and sequenced four other TGGE variants in exon 2 of AGT. These included two new amino acid substitutions (Thr209-->Ile and Leu211-->Arg) that were found only among black PDAY cases. The frequency of the Ile209 mutation was 0.002 and the frequency of the Arg211 was 0.006 in 260 black PDAY cases. The other two TGGE variants were Tyr248-->Cys and a T-->C substitution at nucleotide position 171 that had been identified in previous studies. We also developed restriction isotyping for rapid typing of each AGT variant using PCR amplification and digestion with diagnostic restriction enzymes.
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PMID:Detection and characterization of new mutations in the human angiotensinogen gene (AGT). 760 42

The renin-angiotensin system regulates blood pressure and sodium balance. The angiotensinogen gene which encodes the key substrate within this system has been linked to essential hypertension in White Europeans. It has been suggested that people of West African ancestry may have a different genetic basis for hypertension. In this study we have tested whether there is linkage of the angiotensinogen gene to essential hypertension in African Caribbeans from St. Vincent and the Grenadines. DNA from 63 affected sibling pairs with hypertension was tested for linkage by analyzing whether there was excess allele sharing among siblings genotyped using an angiotensinogen dinucleotide repeat sequence. There was significant support for linkage (T = 3.07, P = 0.001) and association of this locus to hypertension (chi 2 = 50.2, 12 degrees of freedom, P << 0.001). A DNA polymorphism which alters methionine to threonine at position 235 (M235T) within the angiotensinogen peptide has been associated previously with hypertension. However, we found no association of this variant with hypertension in this study. These findings provide support for linkage and association of the angiotensinogen locus to hypertension in African Caribbeans and suggest some similarities in the genetic basis of essential hypertension in populations of different ethnicity.
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PMID:Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. 763 61

Genetic approaches to understanding the pathophysiology of complex human traits, for example, hypertension, can complement physiologic analyses and are likely to improve our ability to treat or prevent the disease. A particularly useful approach is to perform linkage analysis with candidate genes using intermediate phenotypes. This has proven successful so far in identifying two genes involved in hypertension. The first was a fusion gene mutation which linked the regulatory region of the 11B-hydroxylase gene to the coding sequence for the protein of aldosterone synthetase. This mutant gene is responsible for the condition glucocorticoid-remediable aldosteronism (GRA). The intermediate phenotype used was increased levels of the adrenal steroids 18-oxo and hydroxycortisol. The gene for GRA was identified using a pedigree approach. It is likely, to identify other genes in hypertension, that the most appropriate population to be affected would be sib pairs, that is, sibling pairs who both have hypertension. In a recent study the angiotensinogen gene also was linked to hypertension in individuals who had severe or early onset hypertension. In addition, a variant of the angiotensinogen gene, substitution of threonine rather than methionine at codon 235, was specifically associated with hypertension. In a separate study, the T235 homozygote of the angiotensinogen gene was associated with the non-modulating intermediate phenotype of essential hypertension. Since converting enzyme inhibitors appear to correct the specific defect underlying the elevated blood pressure in non-modulators, identification of the gene potentially associated with non-modulation raises the strong possibility that genetic screening will allow for more specific therapy.
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PMID:Genetic approaches to understanding the pathophysiology of complex human traits. 770 3

A molecular variant of the angiotensinogen gene with threonine instead of methionine at position 235 (ie, with M235T polymorphism) has been shown to be associated with essential hypertension in Caucasian populations. The purpose of the present study was to assess whether the M235T polymorphism was associated with essential hypertension in the Japanese population. The study population consisted of 347 subjects selected in our outpatient clinic. The clinical data included in the analyses were sex, age, body mass index, cholesterol level, genotype of the angiotensinogen gene, genotype of the angiotensin-converting enzyme gene, and systolic and diastolic blood pressure. Multiple regression analysis revealed that only body mass index was a predictor of both diastolic and systolic blood pressure in these 347 subjects, but the genotype of the angiotensinogen gene was identified as a predictor of both diastolic and systolic blood pressure in a subpopulation less than 50 years of age. However, in a subpopulation more than 50 years of age, body mass index was the only predictor of both systolic and diastolic blood pressure. Of the 347 subjects, 189 had a technically excellent echocardiogram at the initial observation period. Multiple regression analysis revealed that sex, body mass index, diastolic blood pressure, and genotype of the angiotensin-converting enzyme gene were predictors of left ventricular mass. Although subjects with the TT angiotensinogen genotype had significantly greater left ventricular mass than those with either the TM or the MM genotype, the effects of the genotype of the angiotensinogen gene on left ventricular mass were mainly due to effects on blood pressure.
Hypertension 1995 Apr
PMID:Angiotensinogen gene and blood pressure in the Japanese population. 772 17

To explore the genes responsible for myocardial infarction and restenosis after percutaneous transluminal coronary angioplasty, we performed association studies of the polymorphisms of the angiotensinogen and angiotensin-converting enzyme (ACE) genes. In the first study, normotensive myocardial infarction patients (n = 103) and control subjects (n = 103), who were matched for established risk factors with the myocardial infarction patients, were randomly selected. The angiotensinogen-TT genotype (T indicates threonine instead of methionine at position 235) was more frequent in the myocardial infarction group than in the control group (P < .05). The ACE-DD genotype (D indicates a deletion polymorphism in intron 16) was also more frequent in the myocardial infarction group (P < .0001). The odds ratio estimated by the combined analysis of the angiotensinogen-TT and ACE-DD genotypes (11.2) was markedly increased compared with that estimated separately from the angiotensinogen-TT (1.75) or ACE-DD (4.43) genotype. In the second study, we investigated 91 consecutive patients with acute myocardial infarction who underwent successful direct angioplasty. Combined analysis showed that the angiotensinogen-TT genotype did not enhance the predictability of myocardial infarction from the ACE-DD genotype. In conclusion, the angiotensinogen-TT genotype is a predictor for myocardial infarction, as well as the ACE-DD genotype, and the combined analysis of the angiotensinogen-TT and ACE-DD genotypes further enhanced the predictability of myocardial infarction in Japanese, suggesting its future clinical usefulness.
Hypertension 1995 May
PMID:Enhanced predictability of myocardial infarction in Japanese by combined genotype analysis. 773 32

Several genes, including some encoding components of the renin angiotensin system, are associated with the risk of cardiovascular diseases. There have been reports linking a homozygous deletion allele of the angiotensin converting enzyme (ACE) gene (DD) with an increased risk of myocardial infarction, and some variants of the angiotensinogen gene with an increased risk of hypertension. In a case-control study of a caucasian population from New Zealand, we examined the associations with coronary heart disease (CHD) of ACE DD and of a mis-sense mutation with methionine to threonine aminoacid substitution at codon 235 in the angiotensinogen gene (T235). We studied 422 patients (mean age 62 years, 81% male) with documented CHD (50% with myocardial infarction) and 406 controls without known CHD (frequency-matched to cases by age and sex). Risk factors for CHD were assessed by standard questionnaire, physical examination, and blood tests. Genomic DNA from leucocytes was analysed for various ACE and angiotensinogen alleles. Angiotensinogen T235 homozygotes were at significantly increased risk of CHD generally (odds ratio 1.7, 2 p = 0.008) and of myocardial infarction specifically (1.8, 2 p = 0.009). Adjustment for several risk factors increased the estimate of CHD risk associated with this allele to 2.6 (2 p < 0.001) and the estimate for myocardial infarction risk to 3.4 (2 p < 0.001). By contrast, there was no evidence of a significant increase in the risk of CHD or myocardial infarction among individuals with ACE DD. We conclude that the T235 polymorphism of the angiotensinogen gene is an independent risk factor, which carries an approximately two-fold increased risk of CHD. In this study, however, ACE DD was not associated with any detectable increase in CHD risk.
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PMID:Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease. 763 19


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