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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin angiotensin system is one of the most important humoral factors underlying the mechanism of hypertension. The genes constituting the renin angiotensin system have been expected to be candidates for essential hypertension. DNA polymorphisms of angiotensinogen and angiotensin II type 1 receptor genes are reported to be significantly related with the incidence of human hypertension, but further investigation is needed to clarify the relationship between the genes of the renin angiotensin system and hypertension. The renin angiotensin system exists not only in circulating blood, but also in extrarenal organs and tissues. Tissue renin angiotensin systems in the brain, blood vessels, and adrenal glands are considered to play important roles in the pressor mechanisms in low renin as well as high renin hypertension. Gene expressions of the constituents of the tissue renin angiotensin system are affected in part by circulating angiotensin II, but they are regulated mostly by their own specific control mechanisms in each organ and tissue. In future, laboratory tests in clinical medicine may be necessary to determine the DNA polymorphisms and tissue gene expression of renin angiotensin system, in deciding the diagnosis, prognosis and therapy of hypertension.
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PMID:[Role of renin angiotensin system in the vasopressor mechanisms of hypertension--gene analyses and tissue renin angiotensin system]. 855 76

Genotypic abnormalities of the renin-ANG system have been suggested as a risk factor for the development of diabetic nephropathy. Cleavage of angiotensinogen is the rate-limiting step in the activation of the renin-ANG system. The TT genotype of a polymorphism encoding threonine instead of methionine (M235T) has been associated not only with increased plasma angiotensinogen concentration but also with essential hypertension. In addition, a polymorphism in the angiotensinogen gene substituting methionine for threonine (T174M) has been associated with hypertension in nondiabetic populations. We studied the relationship between these polymorphisms in the angiotensinogen gene in IDDM patients with diabetic nephropathy (121 men, 74 women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years). There was no difference in M235T genotype distribution between IDDM patients with diabetic nephropathy and those with normoalbuminuria: 73/97/25 (37/50/13%) vs. 67/95/23 (36/52/12%) had MM/MT/TT genotypes, respectively. No difference in distribution of T174M genotypes between nephropathic and normoalbuminuric IDDM patients was observed either: 148/44/1 (77/23/0.5%) vs. 141/42/2 (76/23/1%) had TT/TM/MM genotypes, respectively. In patients with nephropathy, systolic blood pressure was higher (161 +/- 22 mmHg [mean +/- SD]) in patients carrying TT genotype of the M235T angiotensinogen polymorphism as compared with patients with MM or MT genotypes (150 +/- 23 mmHg; P = 0.03). We conclude that neither the M235T nor the T174M polymorphism in the angiotensinogen gene contributes to genetic susceptibility to diabetic nephropathy in white IDDM patients, whereas the TT genotype of the M235T is associated with elevated blood pressure in patients with diabetic nephropathy.
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PMID:Angiotensinogen gene polymorphisms in IDDM patients with diabetic nephropathy. 859 44

The allele 235T (a threonine in place of a methionine at position 235) of angiotensinogen has been found to be associated with a predisposition to essential hypertension. We investigated whether this allele also confers increased susceptibility to nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). A group of 380 patients who had had IDDM for 15 to 20 years were genotyped at the angiotensinogen 235 locus. Included were 75 patients with normoalbuminuria (albumin excretion rate < 30 micrograms/min), two series of patients with microalbuminuria (n = 30 and n = 136), and two series with overt proteinuria (n = 41 and n = 98). Allele 235T frequency was higher among cases with microalbuminuria (0.41 in the two series combined) or overt proteinuria (0.40) than in the normoalbuminuria group (0.36). However, this difference was not statistically significant with this sample size (chi 2 = 1.2, P = NS with 2 df). Under a recessive model, allele 235T homozygotes had a 1.6-fold risk of developing nephropathy relative to carriers of other genotypes, but this value was not significantly different from 1(95% CI = 0.8 to 3.5). The strength of the association did not improve after stratification by degree of glycemic control. With respect to the hypertension in these IDDM patients, no association with allele 235T was found. Allele 235T frequencies in normotensive and hypertensive individuals were 0.363 and 0.353, respectively, among normoalbuminuric IDDM individuals (chi 2 = 0.01, P = NS) and 0.411 and 0.414 among microalbuminuric IDDM subjects (chi 2 = 0.0, P = NS). We conclude that the angiotensinogen polymorphism M235T might influence susceptibility to nephropathy in insulin-dependent diabetes, but its effect, if any, is rather small and independent of hypertension.
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PMID:Angiotensinogen polymorphism M235T, hypertension, and nephropathy in insulin-dependent diabetes. 862 Dec 7

A number of recent studies have implicated the angiotensinogen gene in the aetiology of essential hypertension in Caucasian, Japanese and African Caribbean subjects. We have genotyped 153 healthy white Caucasian subjects at a dinucleotide repeat polymorphism and seven diallelic sites in the coding or flanking regions of the angiotensinogen gene, including one polymorphism not previously studied. We have also documented patterns of linkage disequilibrium between polymorphisms. There is evidence of variation in the frequency of several mutations when compared with published results from other Caucasian control populations, possibly due to cryptic ethnic differences between these groups. This should be considered in the design and interpretation of studies of the angiotensinogen gene.
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PMID:DNA polymorphisms and linkage disequilibrium in the angiotensinogen gene. 869 41

Recent studies have suggested that an inherited predisposition to essential hypertension may increase susceptibility to nephropathy for patients with IDDM. Essential hypertension has been linked to the angiotensinogen (AGT) gene in genetic linkage studies in American and European populations. A molecular variant (M235T), which has a functional effect, has been described with highest plasma AGT levels being associated with the TT genotype. In a case-control study, we have evaluated the role of this functional genetic marker in patients with IDDM and nephropathy and in IDDM patients without nephropathy. We studied 195 IDDM patients, of whom 95 had established diabetic nephropathy; the remaining 100 patients, who had no evidence of microalbuminuria, served as control subjects. All patients were whites born in Northern Ireland. The point mutation in the AGT gene was analyzed using restriction typing. The background frequency of the M235T variant was assessed in 80 healthy blood donors, and the TT genotype was present in 9%. This genotype occurred in 8% of control IDDM patients without nephropathy and 19% of IDDM patients with nephropathy (P = 0.025). The odds ratio for diabetic nephropathy associated with the TT genotype was 2.7 (95% CI 1.04-7.52). There was no relationship between blood pressure and AGT genotypes in the control group. We cannot exclude the possibility that the observed association in the nephropathy group is due to an association between AGT genotype and hypertension. This evidence may help to explain the predisposition to diabetic nephropathy afforded by hypertension and merits further investigation.
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PMID:A molecular variant of angiotensinogen is associated with diabetic nephropathy in IDDM. 877 23

A recent study reported a significant relationship between a T704-->C (Met235-->Thr) variant in exon 2 of the angiotensinogen gene in adults and essential hypertension. In the present study, this variant was detected in 131 Japanese children using a polymerase chain reaction. The allele frequency of the variant was 0.76. The genotype frequency of the homozygote for the allele was 0.59, and children who were homozygous had higher systolic blood pressure than those with the other two genotypes. No relationship was found between children's polymorphism and a family history of essential hypertension. These findings suggest that this molecular variant of the angiotensinogen gene may play some role in the regulation of blood pressure in Japanese children.
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PMID:Analysis of Met235 to Thr variant of the angiotensinogen gene in relation to the blood pressure and family history of essential hypertension in Japanese children. 884 May 36

Although essential hypertension has long been recognized to involve a strong genetic predisposition, the genes that increase susceptibility remain virtually unknown. With recent advances in molecular biology and statistical methods, it has become feasible to study candidate genes which may contribute to the pathogenesis of essential hypertension in humans. Recently, the angiotensinogen (AGT) locus was demonstrated to exhibit genetic linkage and association to essential hypertension and to preeclampsia. While the statistical evidence that mutations of the AGT gene or a neighboring gene contribute to the development of hypertension is strong, the exact mechanism(s) by which these mutations affect the regulation of blood pressure (BP) is unknown. Increasing attention is now being focused on elucidating this mechanism(s).
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PMID:Role of angiotensinogen in the genetics of essential hypertension. 884 59

Although it has been recognized for almost 70 years that there is a substantial genetic component to the pathogenesis of hypertension, only recently have systematic efforts been made to identify the responsible genetically determined mechanisms. In the case of several rare syndromes, spectacular progress has been made in identifying the underlying molecular mechanisms responsible for the clinical expression. Glucocorticoid-suppressible aldosteronism and Liddle's syndrome, each inherited as an autosomal-dominant condition, complete the list. In the case of randomly selected patients and families with essential hypertension, inheritance involves many genes and progress has been far more modest. Probably the most promising lead has involved the genes governing the structure of angiotensinogen, the substrate in the renin reaction. Linkage has been established and confirmed. At the moment, however, neither the relation of the genetic abnormality to the underlying mechanisms, nor the contribution of this abnormality to hypertension in the individual patient, has been defined. We know less about other candidate genes, with the exception of studies that rigorously ruled out a contribution. The development of the concept of the "intermediate phenotype," a physiological feature that makes it possible to identify a homogeneous subpopulation, should help to sort out many of these issues. Unfortunately, the identification and characterization of intermediate phenotypes is substantially more difficult at the moment than are the genetic studies, and so progress is likely to be slow. The field is complicated by the reporting of claims made on the basis of small patient samples. In the case of polymorphisms in the angiotensin-converting enzyme gene as a risk factor for tissue injury, for example, substantial follow-up studies have systematically failed to confirm the original report, which was based on a small patient sample. The fact that the same DNA collection is likely to be examined many times for multiple gene candidates creates a setting in which type I errors are likely, and so we are likely to see many more examples. Caveat lector. Again, the development of relevant intermediate phenotypes will make the spurious association less likely.
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PMID:Genes, hypertension, and intermediate phenotypes. 888 70

Advances in molecular medicine and pharmacology have allowed clinicians to critically reassess the renin-angiotensin system. Angiotensin II (AII) participates in the control of cardiovascular function and electrolyte balance, and plays a part in the regulation of cellular oncogenes and the expression of growth factors. The expression of the proteins of the renin-angiotensin system in organs other than the kidneys suggests that these diverse actions are associated with the peptide in the local environment. Tissue renin-angiotensin activity has prompted the investigation of alternate pathways for the production of AII and characterization of novel forms of angiotensin peptides that counteract the vasoconstrictor and proliferative actions of AII. The heptapeptide angiotensin-(1-7) appears to be critically involved in regulating the angiotensinogen activity of AII through stimulation of vasodilator prostaglandins and release of nitric oxide. Study in this area has been accelerated by the identification of receptors that convey the actions of angiotensin peptides at the cellular level and the pharmacologic characterization of agents that inhibit the ability of AII to bind to target receptors. The introduction of a new class of orally active AII-receptor blockers has provided a specific test of the role of AII in the development of essential hypertension and the potential for improved therapy for hypertension and cardiac and vascular sequelae.
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PMID:Pathologic consequences of increased angiotensin II activity. 895 64

The candidacy of angiotensinogen for a role in the genetic basis of hypertension is supported by the observation that plasma angiotensinogen levels track with raised blood pressure through families. In addition, transgenic mice with overexpression of a rat angiotensinogen gene develop hypertension, and knockout mice with a disrupted gene and absent angiotensinogen production develop low blood pressure. There are now two studies in populations of white European origin and one in African Caribbeans providing support for a role of the angiotensinogen gene locus in human essential hypertension.
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PMID:Angiotensinogen in human essential hypertension. 895 9


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