Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Essential hypertension probably results from combinations of genetic variations, not necessarily the same in all afflicted persons, which individually may not cause sufficient deviation from normality to be significantly harmful. Genes contributing to hypertension are being sought by analytic experiments aimed at identifying candidate genes associated or segregating with the phenotype in humans and animals and by synthetic experiments in which changes are made in candidate genes in animals and their effects on blood pressure are determined. We have used gene targeting to vary the amounts of angiotensinogen and angiotensin-converting enzyme (ACE) synthesized from their genes (Agt and Ace). These "gene titration" experiments establish that changes in Agt gene expression cause changes in the blood pressures of mice. Surprisingly, quantitative changes in Ace gene expression over a threefold range do not affect blood pressures. Computer simulations with a simple version of the renin-angiotensin system predict that changes in Agt function alter the steady state levels of both angiotensin I (Ang I) and angiotensin II (Ang II). In contrast, modest changes in Ace function alter Ang I levels considerably but scarcely affect Ang II levels. Simulations over the ranges of ACE levels that can be achieved with ACE inhibitors predict that Ang II levels will decrease only when Ang I levels have plateaued. Comparisons of the computer simulations with our genetic experiments and with prior work of others using wide dose ranges of ACE inhibitor show a satisfactory agreement and help reconcile the apparent contradictions between the genetic and pharmacological experiments.
 ...
PMID:Theodore Cooper Memorial Lecture. A mouse view of hypertension. 940 47

The angiotensinogen (AGT) gene M235T variant is associated with essential hypertension and elevated plasma AGT concentrations, although the underlying mechanisms are unknown. Recent studies have suggested that AGCE 1 (human AGT gene core promoter element 1) located in the 5' upstream core promoter region (position -25 to -1) of the human AGT gene has an important part in the expression of AGT mRNA by binding with transcription factor AGCF 1 (human AGT gene core promoter element binding factor 1), and a mutation at -20 from adenine to cytosine (A-20C) increases the level of expression of this transcript. We therefore examined subjects with this mutation to study the association with increased plasma AGT concentrations and with essential hypertension. One hundred eighty-eight subjects receiving no antihypertensive medication were examined with regard to the correlation between A-20C and plasma AGT concentrations, and 234 subjects were studied with respect to the association between A-20C and essential hypertension. A-20C was determined by polymerase chain reaction-restriction fragment length polymorphism analysis with EcoOR 109I. Multiple regression analysis showed a weak but significant correlation between A-20C and plasma AGT concentrations (P=.047) and essential hypertension (P=.049). The results suggest that A-20C may underlie the increase in plasma AGT concentrations and be involved in the development of essential hypertension.
 ...
PMID:Essential hypertension and 5' upstream core promoter region of human angiotensinogen gene. 940 48

The renin-angiotensin system plays a major role in regulating blood pressure and maintaining electrolyte and volume homeostasis. Previously, the angiotensinogen gene, which encodes the key substrate for renin within this system, has been reported linked to and associated with essential hypertension in White Europeans, African-Caribbeans, and Japanese. Therefore, we investigated whether the angiotensinogen gene might be similarly implicated in the pathogenesis of essential hypertension in Chinese by carrying out linkage analysis in 310 hypertensive sibling pairs. Genotypes for two diallelic DNA polymorphisms observed at amino acid residues 174 (T174M) and 235 (M235T) within the coding sequence and for two highly informative dinucleotide (GT)-repeat sequences (one in the 3' flanking region, and one at a distance of 6.1 cM from the gene) were determined. Affected sibpair analysis conducted according to three different algorithms (S.A.G.E./SIBPAL, MAPMAKER/ SIBS, and APM methods) revealed no evidence for linkage of the angiotensinogen gene to hypertension. Our data indicate that molecular variants of this gene do not appear to contribute materially to the pathogenesis of primary hypertension among Chinese (a notion supported by concomitant, direct estimates of power), and that the disease relevance of this gene may vary therefore depending on ethnicity.
 ...
PMID:Angiotensinogen gene and hypertension in Chinese. 942 81

There are four methods for detecting the angiotensinogen gene Agt T235/M235; 1) allele-specific oligonucleotide hybridization (PCR-ASO); 2) mutagenically separated PCR (MS-PCR) using three primers to amplify all possible alleles in on PCR reaction; 3) restriction endonuclease Tth111-I; 4) SfaN-I digestion method using mismatched primer for the PCR (modified PCR-RFLP). Two of these four methods have been used in Japanese studies. The reported allelic frequencies of Agt T235/M235 in normal controls in the Japanese population are around 0.75-0.84/0.25-0.16 (as a whole 0.80/0.20) by PCR-ASO and 0.70-0.65/0.30-0.35 (as a whole 0.67/0.33) by the modified PCR-RFLP (Tth111-I). The present study tested how these methods contribute to the differences in Agt T235/M235. By PCR-ASO, the genotypes could be clearly determined. However, it is hard to complete every digestive reaction under the experimental conditions described for modified PCR-RFLP (Tth111-I). Thus, for studying Agt T235/M235, PCR-ASO or some method other than PCR-RFLP (Tth111-I) can be recommended. Our findings suggest that the allele frequency of Agt T235/M235 in the normal Japanese population is closer to 0.75-0.84/0.25-0.16. Although a strong association was reported between the Agt T235 allele and essential hypertension or myocardial infarction, using the modified PCR-RFLP (Tth111-I), two of three studies using PCR-ASO found no or only a weak association. The relationship between the Agt T235 allele and essential hypertension or myocardial infarction in the Japanese population needs to be assessed.
 ...
PMID:Angiotensinogen gene polymorphism of threonine/methionine at position 235-potential problems of the modified restriction endonuclease (Tth111-I) digestion method. 944 44

In the last decade, two types of genes participating in the etiology of hypertension have been identified. The primary genes or blood pressure regulators are those that codify enzymes (renin, kallikrein, kininase, aminopeptidase), hormones (angiotensins, vasopressin, aldosterone, prostaglandins, and atrial natriuretic peptide) and substrates (angiotensinogen and kininogen). They cause arteriolar vasodilation or vasoconstriction or sodium retention in the extravascular space. Allelic polymorphisms associated to essential hypertension have been described. The secondary genes are those that produce hereditary diseases of low prevalence, associated to hypertension in 20 to 80% of patients (polycystic kidney disease, pheochromocytoma, adrenal hyperplasia, hereditary nephritis). Forty genes located in all chromosomes, that are dominantly, recessively or X-linked transmitted, have thus far been identified. Chromosomal maps with all genic loci are presented.
 ...
PMID:[The genes of human hypertension]. 946 Feb 75

Different family and case-control studies support genetic linkage and association at the human angiotensinogen (AGT) locus with essential hypertension. To extend these previous observations, a European collaborative study of nine centers was set up to create a large resource of affected sibling pairs. The AGT locus was studied using a highly polymorphic dinucleotide repeat in the 3'-flanking region of the gene in 350 European families, comprising 630 affected sibling pairs. Statistical analyses using two different methods did not show any evidence for linkage either in the whole panel or in family subsets selected for severity or early onset of disease. Although several arguments from association studies suggest a role of the AGT gene in essential hypertension, this large family study did not replicate the initial linkage reported in smaller studies. Our results highlight the difficulty of identifying susceptibility genes by linkage analysis in complex diseases.
 ...
PMID:Evaluation of the angiotensinogen locus in human essential hypertension: a European study. 949 53

The main task in hypertension research is to explain genetic causes of a raised blood pressure. It is anticipated that advances in this area will promote not only a better understanding of the pathophysiology of hypertension but will make a more aimed approach to early diagnosis, prevention and therapy of essential hypertension possible. The greatest problems in investigations of the heredity of hypertension are; a) in cardiovascular control mechanisms several genes participate; b) factors of the external environment which act on a long-term basis interfere with the relationship of the genotype and phenotype individually, within the family and regionally; c) the blood pressure is a continuous variable and the definition of the phenotype of hypertension is inaccurate; d) inadequate number of family members where hypertension segregates. New methods in molecular biology and statistical genetics made it possible to assess a number of highly polymorphous genetic signs in several candidate genes and the subsequent investigation of their possible role in the pathogenesis of hypertension. The majority of hitherto accomplished studies was concentrated on genes coding different components of the renin-angiotensin system: renin, ACE, angiotensinogen and angiotensin II receptors. So far the most promising, though not consistent, results were obtained for angiotensinogen and the insulin receptor. Work focused on the relationship of the polymorphism of genes for ANF, growth hormone and kallikrein to essential hypertension is negative. The genetic heterogeneity of the human population, physiological differences in the genesis of high blood pressure in different ethnical groups and inaccurate measurements of specific phenotypes can contribute to different results of different studies.
 ...
PMID:[Molecular genetics methods in the study of hereditary essential hypertension]. 951 Dec 64

This study examined the association between the development of nephropathy in non-insulin-dependent diabetes mellitus (NIDDM) patients and M235T polymorphism in the angiotensinogen gene. White NIDDM patients with diabetic nephropathy (case subjects, n = 117) and patients without any evidence of nephropathy and > or = 10 years of NIDDM (control subjects, n = 125) were selected from among patients of the Joslin Diabetes Center and examined. In addition to a standardized examination, blood was drawn for DNA and determination of M235T genotypes at the angiotensinogen locus. For the angiotensinogen gene, the frequency of the genotype 235T/235T, known to be associated with essential hypertension, was higher among case subjects with nephropathy than in control subjects without this complication. This difference, expressed as the odds ratio for nephropathy among 235T/235T homozygotes in comparison with all other genotypes, was 2.2 (95% confidence interval, 1.1 to 4.4). The difference, however, was confined to men (odds ratio, 4.8; 95% confidence interval, 1.5 to 14.9), with the distribution of genotypes in case and control subjects being equal among women (odds ratio, 1.1). DNA polymorphism M235T in the angiotensinogen gene, which is associated with higher expression of this gene, contributes to the risk of diabetic nephropathy in NIDDM men but not in women.
 ...
PMID:Gender-specific association of M235T polymorphism in angiotensinogen gene and diabetic nephropathy in NIDDM. 953 11

To prove whether the interaction between insertion/deletion (I/D) angiotensin I converting enzyme (ACE) and M235T angiotensinogen (AGT) gene polymorphic alleles could contribute to causing essential hypertension, we examined subjects from the Czech Republic (365 Caucasians total; 202 normotensives and 163 hypertensives). Subjects were genotyped for insertion/deletion polymorphism of ACE (I/D ACE, intron 16) and for M235T polymorphism of angiotensinogen gene (AGT, exon 2) by means of the polymerase chain reaction (PCR) method. The case-control approach was used. Fisher's exact test followed by Holmes's test to overcome the problem of multiple comparisons were used for the statistical analysis of data. No association of single gene allelic variants with essential hypertension was found in our population. Having compared only double homozygote combinations, the association of the DDMM genotype with essential hypertension was proven (P = 0.0081). To the contrary, IITT (P = 0.0086) was found more frequently in normotensive subjects. We conclude that the interaction of the I/D ACE and M235T AGT polymorphic alleles can contribute to essential hypertension, despite the absence of single gene associations with the condition.
 ...
PMID:Angiotensin I-converting enzyme and angiotensinogen gene interaction and prediction of essential hypertension. 960 78

The molecular variants M235T and T174M of the angiotensinogen gene have been linked to essential hypertension in some populations, but there are discrepancies about this association in other studies. We studied 75 patients with essential hypertension (BP > 160/100 mm Hg) from our outpatient clinic, aged 55+/-1 years, 30 men, systolic BP 182+/-2.5, diastolic BP 109+/-1 mm Hg (mean +/- SEM), and a family history of the disease. Target organ damage was evaluated by measuring urinary albumin excretion rate, left ventricular hypertrophy, and fundoscopy. As a control group, 75 healthy subjects with BP < 130/85 mm Hg and with no family history of cardiovascular disease were selected. M235T and T174M angiotensinogen genotypes were determined by PCR and subsequent digestion of the products with SfaNI and NcoI, respectively. The frequency (q) of genotypes of the variant M235T in the patients with essential hypertension was MM 0.31, MT 0.41, and TT 0.28, not significantly different (P = .93) from that of the controls (MM 0.28, MT 0.44, and TT 0.28). For the variant T174M, the genotype frequencies in hypertensives were TT 0.83, TM 0.15, and MM 0.02, which was not significantly different (P = .89) from that of the controls (TT 0.86, TM 0.12, and MM 0.02). Similarly, there was no evidence for association between angiotensinogen genotypes and hypertension in subjects aged < or = 40 years old (n = 24) or with severe (stage III) hypertension (n = 31). Within the group of patients with essential hypertension, there were no differences in genotype distribution between patients with and without retinopathy (n = 31), left ventricular hypertrophy (n = 37), or microalbuminuria (n = 14). This study shows that M235T and T174M variants are not associated either with essential hypertension or with target organ damage in a Spanish sample.
 ...
PMID:Angiotensinogen gene M235T and T174M polymorphisms in essential hypertension: relation with target organ damage. 960 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>