angiotensinogen and Syndrome

The knowledge of the genetic bases of hypertension has improved over the last decade; this area of research has high priority due to the high incidence of hypertension and its impact on public health. Monogenetic mineralocorticoid hypertension syndromes are associated with suppressed plasma renin activity due to excessive activation of the mineralocorticoid pathway. We review the pathophysiology, phenotype, and method of diagnosis for familial hyperaldosteronism type I and type II, hypertensive forms of congenital adrenal hyperplasia, 11beta-hydroxysteroid dehydrogenase type 2 deficiency, Liddle's syndrome, an activating mutation of the MR, and glucocorticoid resistance. We also review some genes that could contribute to essential hypertension.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 2; 11-beta-Hydroxysteroid Dehydrogenases; Adrenal Hyperplasia, Congenital; Angiotensinogen; Drug Resistance; Epithelial Sodium Channels; Glucocorticoids; Humans; Hyperaldosteronism; Hypertension; Mineralocorticoid Excess Syndrome, Apparent; Peptidyl-Dipeptidase A; Phenotype; Receptor, Angiotensin, Type 1; Receptors, Mineralocorticoid; Syndrome

For the past decade, hypertension research has shifted strongly in the direction of molecular genetics. The success stories are the monogenic hypertensive syndromes. Classic linkage analyses has located the responsible genes for glucocorticoid-remediable aldosteronism, Liddle syndrome, and apparent mineralocorticoid excess. The genes have been cloned and their function elucidated. Other monogenic syndromes are currently being intensively studied. However, in the area of primary hypertension, the successes have relied on the candidate gene approach. Allelic variants in the genes for angiotensinogen, alpha-adducin, beta2-adrenergic receptor, the G-protein beta3-subunit and the T594M mutation in the beta-subunit of the epithelial sodium channel have been identified; however, the importance of these allelic variants to primary hypertension as a whole, is not yet clear. A variant in the angiotensin-converting enzyme gene could not, initially, be convincingly associated with hypertension, but more recent analyses suggest an influence of the deletion allele on blood pressure in men, but apparently not in women. In all likelihood we are dealing with many genes with small effects. Affected sibling pair linkage analyses will probably not be successful in identifying the loci of these genes. To find new genes, novel approaches will be necessary, including searching for quantitative trait loci linked to blood pressure in normotensive persons, haplotype sharing methodology in trios and family units, the use of better study designs, and the investigation of isolated populations. Finally, rethinking the phenotype 'hypertension' and its intermediates must also receive priority.

Topics: Angiotensinogen; Calmodulin-Binding Proteins; Female; Fingers; GTP-Binding Proteins; Humans; Hyperaldosteronism; Hypertension; Male; Mineralocorticoids; Molecular Biology; Mutation; Peptidyl-Dipeptidase A; Receptors, Adrenergic, beta-2; Sodium Channels; Syndrome

In the most exciting genetic advances in the diagnosis of essential hypertension, genes responsible for three distinct forms of low-renin hypertension have been identified. Two of these forms are dominant: glucocorticoid remediable hypertension (a new gene created by the fusion of the 11 beta-hydroxylase and aldosterone synthase genes) and Liddle's syndrome (a defect in the epithelial sodium channel). One of the forms is recessive: the syndrome of apparent mineralocorticoid excess (a defect in renal 11 beta-hydroxysteroid dehydrogenase). The role of more than 20 other genes in causing hypertension has been assessed with variable findings. The most convincing evidence supports a role for the angiotensinogen gene, where linkage has been documented and an association with an intermediate phenotype of hypertension (nonmodulation) has been reported.

Topics: Angiotensinogen; Animals; Genetic Linkage; Humans; Hypertension; Peptidyl-Dipeptidase A; Phenotype; Renin-Angiotensin System; Syndrome

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.

Topics: Angiotensinogen; Atrial Natriuretic Factor; Genes, Dominant; Humans; Hyperaldosteronism; Hypertension; Nitric Oxide Synthase; Peptidyl-Dipeptidase A; Phenotype; Polymorphism, Genetic; Racial Groups; Renin-Angiotensin System; Syndrome

In the past few years, a number of key insights have been made concerning the genetic basis of hypertension and blood pressure regulation. The genes responsible for two Mendelian forms of hypertension, glucocorticoid-remediable aldosteronism and Liddle's syndrome, were identified. In addition, research into the role of the renin-angiotensin system in blood pressure regulation has further implicated the angiotensinogen and angiotensin-converting enzyme loci in hypertension and its complications, such as myocardial infarction. Finally, several new candidate genes for hypertension have been identified through the use of genome scanning and contemporary gene expression assays in model organisms.

Topics: Angiotensinogen; Animals; Blood Pressure; Disease Models, Animal; Gene Expression; Genetic Linkage; Genetic Variation; Genome; Glucocorticoids; Humans; Hyperaldosteronism; Hypertension; Hypokalemia; Mice; Mice, Transgenic; Peptidyl-Dipeptidase A; Rats; Receptors, Angiotensin; Syndrome

Hypertension occurred in 50% obstructive sleep apnea-hypopnea syndrome (OSAHS) patients meanwhile OSAHS occurred in 30% hypertension patients. The present study aimed to explore the molecular mechanism of GATA2-EDN1-AGT induced hypertension in the development of obstructive sleep apnea-hypopnea syndrome. OSAHS patients (56 cases: 36 cases of male, 20 cases of female, 42~60 years old) were divided into two groups (case group: patients with hypertension monitored by 24 h ambulatory blood pressure and polysomnography; control group: patients without hypertension). Wistar rats were used to establish the OSAHS model (narrow pharyngeal cavity). PaO2 and PaCO2 of patients and rats were measured by an automatic blood gas analyzer. The profile of total protein in the OSAHS group and normal group was evaluated. Protein-protein-interaction (PPI) was carried out to show all matter proteins related. The levels of EDN-1, AGTII and atrial natriuretic peptide (ANP) in blood samples of patients and rats were analyzed by enzyme-linked immunosorbent assay (ELISA). The expression of GATA2, EDN1, endothelin-converting enzyme 1 (ECE-1) and AGTⅡ was measured. The results showed that SaO2 and AHI were positively associated with systolic pressure (P<0.05) in OSAHS patients. There was no correlation among other indexes (P>0.05). It was also observed that GATA2 had a strong relationship with AGTⅡ and EDN1. The results of ELISA presented that the levels of EDN1, AGTⅡ and ANP in the OSAHS group of human and animal models were significantly increased (P<0.05). The results of immunochemistry showed that the expression of GATA2 and AGTⅡ in the vascular of OSAHS group was upregulated manifestly (P<0.05). It was concluded that OSAHS can induce AHI, which increases hypertension via the GATA2-EDN1-AGT Ⅱ axis.

Topics: Angiotensinogen; Animals; Atrial Natriuretic Factor; Blood Pressure Monitoring, Ambulatory; Endothelin-1; Female; GATA2 Transcription Factor; Hypertension; Male; Rats; Rats, Wistar; Sleep Apnea, Obstructive; Syndrome

Pink urine syndrome (PUS) is attributed to the precipitation of uric acid caused by low urinary pH (U-pH). However, the reasons for the lower U-pH are unclear.. To investigate the occurrence of PUS and verified the cause of U-pH reduction.. Participants comprised 4,940 students who had undergone a physical examination. Data on the presence [PUS (+)] or absence [PUS (-)] of PUS, as well as age, gender, body mass index (BMI), blood pressure (BP), heart rate (HR), and U-pH were collected. Of these participants, 300 randomly selected individuals were evaluated for their waist circumference, as well as their levels of urinary C-peptide, angiotensinogen, methylglyoxal, thiobarbituric acid-reactive substances (TBARS), and Na(+) excretion. Independent risk factors of lower U-pH were decided by a multiple-regression analysis.. PUS was observed in 216 students (4.4 %). A greater number of men comprised the PUS (+) group compared with the PUS (-) group, and subjects in this group had high BMI, BP, and HR values, as well as low U-pH. A logistic regression analysis revealed that the BMI and U-pH were independent risk factors for PUS (+). The decrease of U-pH was closely related to the progress of chronic kidney disease (CKD). BMI value was related to PUS (+) in the CKD (-) subjects. On the other hand, low U-pH was related to PUS (+) in the CKD (+) subjects. All factors other than HR showed a significant negative correlation with U-pH. However, multiple-regression analysis revealed that TBARS and angiotensinogen were independent risk factors.. Obesity and lower U-pH were each independently related to PUS, whereas increased intrarenal oxidative stress and exacerbation of the renin-angiotensin system activation were associated with the lowering of U-pH. U-pH low value is related to potential CKD.

Topics: Adolescent; Angiotensinogen; Asian People; Blood Pressure; Body Mass Index; Color; Female; Humans; Hydrogen-Ion Concentration; Male; Obesity; Pyruvaldehyde; Risk Factors; Syndrome; Thiobarbituric Acid Reactive Substances; Uric Acid; Urologic Diseases; Waist Circumference; Young Adult

To explore the relationship between angiotensinogen (AGT) gene M235T and TCM syndrome type in essential hypertension (ET) patients.. The gene mutation frequency of AGT M235T in 168 ET patients and 42 nomotensive (NT) subjects were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.. There was a significant difference in AGT M235T gene mutation between patients of Gan-fire exuberant type and those of yin-yang deficiency type (P < 0.01), homozygote type TT appeared with higher frequency. Multivariate regression linear analysis demonstrated that the genotypes of AGT M235T was correlated with the prognosis of ET to a certain degree.. Gene mutation of AGT M235T may be associated with the genesis and development of ET, and the TCM syndrome type of ET has its own intrinsic molecular biological background.

Topics: Adult; Aged; Angiotensinogen; China; Diagnosis, Differential; Female; Humans; Hypertension; Male; Medicine, Chinese Traditional; Middle Aged; Multivariate Analysis; Mutation; Polymorphism, Genetic; Syndrome

It has been reported that patients with mitral valve prolapse syndrome (MVPS) also have a disorder in autonomic or neuroendocrine function which can cause many related symptoms. Although a potential role of the reninangiotensin system in the pathogenesis of MVPS has been addressed, the role of the angiotensinogen (AGT) genetic variant in MVPS has not been studied. Thus, a case-controlled study was performed to investigate the possible relationship between AGT gene polymorphisms and MVPS.. A total of 100 patients with MVP diagnosed by echocardiography and 100 age- and sex-matched normal control subjects was studied. AGT gene M235T and T174M polymorphisms were identified by polymerase chain reaction-based restriction analysis.. There was a significant difference in the distribution of AGT gene M235T genotypes (p <0.001) and allelic frequencies (p <0.001) between MVPS cases and controls. An Odds Ratio (OR) for risk of MVPS associated with M235T TT genotype was 8.55 (95% CI 4.51-16.18). An OR for risk of MVPS associated with the T allele at the M235T locus of the AGT gene was 3.27 (95% CI 2.05-5.22). The T174M polymorphism of AGT gene showed no association with MVPS (p = 0.94).. These findings suggest that the M235T polymorphism of the AGT gene is associated with MVPS in the Chinese population of Taiwan. The association of the TT genotype with MVPS is more noteworthy than an overall increase in the frequency of the T allele at the M235T locus.

Topics: Adolescent; Adult; Aged; Angiotensinogen; Asian People; Case-Control Studies; Echocardiography, Doppler, Color; Female; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Prolapse; Polymorphism, Genetic; Risk Factors; Severity of Illness Index; Syndrome; Taiwan

Twelve patients with cirrhosis, refractory ascites, and varying degrees of renal failure (creatinine clearance, 5 to 44 ml/min) were studied before and up to 2 weeks following peritoneovenous shunt. Creatinine clearance increased 60% or more in seven patients (group I) and 22% or less in five patients (group II). There were no significant differences in maximum urine output or sodium excretion between groups (group I, 4,272 ml/14 hr, 372 mEq/24 hr; group II, 3,722 ml/24 hr, 255 mEq/24 hr). Aldosterone and renin concentrations were higher in group I and showed a greater decrease after shunting. Renin substrate levels also were higher in group I and rose following shunt insertion, while group II remained low. Ascitic fluid was found to contain renin substrate in concentrations of approximately 25% to 50% of plasma concentrations. Patients with the greatest increase in creatinine clearance showed the largest rise in substrate concentration and fall in renin and aldosterone secretion, suggesting a dynamic relationship between these factors. That a diuresis could occur without significant change in these parameters in five of 12 patients suggests independent control mechanisms for renal salt and water excretion and glomerular filtration in the ascitic patient.

Topics: Aldosterone; Angiotensinogen; Ascites; Creatinine; Diuresis; Fatty Liver; Glomerular Filtration Rate; Kidney; Liver Cirrhosis, Alcoholic; Natriuresis; Peritoneum; Renin; Syndrome; Veins