Molecular basis of human hypertension: Role of angiotensinogen
CellPublished 1 October 1992
Xavier Jeunemaı̂tre, Florent Soubrier, Yuri Kotelevtsev, Richard P. Lifton, Christopher S. Williams, Anne Charru
Citations1,861
SJR quartileQ1
SJR score22.61
SNIP7.62
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TL;DR
Evidence of genetic linkage between the angiotensinogen gene (AGT) and hypertension is obtained, association of AGT molecular variants with the disease is demonstrated, and significant differences in plasma concentrations of angiotENSinogen among hypertensive subjects with different AGT genotypes are found.
Abstract
Essential hypertension is a common human disease believed to result from the interplay of multiple genetic and environmental determinants. In genetic studies of two large panels of hypertensive sibships from widely separated geographical areas, we obtained evidence of genetic linkage between the angiotensinogen gene (AGT) and hypertension, demonstrated association of AGT molecular variants with the disease, and found significant differences in plasma concentrations of angiotensinogen among hypertensive subjects with different AGT genotypes. The corroboration and replication afforded by these results support the interpretation that molecular variants of AGT constitute inherited predispositions to essential hypertension in humans.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
GeneticsMapping mendelian factors underlying quantitative traits using RFLP linkage maps.
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Proceedings of the National Academy of SciencesDetection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms.
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NatureA chimaeric llβ-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension
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JAMAHypertension: Pathophysiology, Diagnosis, and Management
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NatureFulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene
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PubMedLinkage strategies for genetically complex traits. II. The power of affected relative pairs.
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The power to detect disease-susceptibility loci through linkage analysis using pairs of affected relatives and affected-unaffected pairs is examined and simultaneous use of multiple markers diminishes the effect of recombination and allows for localization of the disease-magnifying locus.
CellGenetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat
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NatureClose linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus
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GenomicsCentre d'Etude du polymorphisme humain (CEPH): Collaborative genetic mapping of the human genome
591 Citations1990J Dausset, Howard M. Cann +4 more
Journal of Clinical InvestigationAngiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat.
479 Citations1986Duncan J. Campbell, Joel F. Habener
A demonstration of a widespread tissue distribution of angiotensinogen mRNA may indicate a similarly widespread distribution of local angiotENSin systems that are independent of the circulating renin-angiotens in system.
Genetic EpidemiologyA comparison of sib‐pair linkage tests for disease susceptibility loci
399 Citations1985William C. Blackwelder, Robert C. Elston +1 more
It is shown it is valid to use the information from all possible sib pairs as though they came from separate families when data on sibships of size three or larger are available, though more power may be obtained if different weights are given to the different sibship sizes.
PubMedLinkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs.
390 Citations1990Neil Risch
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Nature GeneticsAbsence of linkage between the angiotensin converting enzyme locus and human essential hypertension
382 Citations1992Xavier Jeunemaı̂tre, Richard P. Lifton +3 more
The localization of the ACE gene on the genetic map of chromosome 17 is reported, and an extremely polymorphic marker at the human growth hormone (hGH) locus which shows no recombination with ACE is identified which suggests that mutations at the ACE locus do not commonly contribute to the pathogenesis of hypertension.
Journal of HypertensionAbnormalities of glucocorticoid metabolism and the renin???angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure
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The combined biochemical and genetic findings suggest that abnormalities of glucocorticoid metabolism and the renin-angiotensin system may help to explain genetic predisposition to high blood pressure.
HypertensionRelation between blood pressure and renin, renin substrate, angiotensin II, aldosterone and urinary sodium and potassium in 574 ambulatory subjects.
298 Citations1979W. Gordon Walker, Paul K. Whelton +3 more
Renin substrate was highly and positively correlated with diastolic blood pressure but all other components of the renin-aldosterone system exhibited a significant negative correlation with blood pressure, raising the possibility of a significant pathogenetic relationship between potassium and high blood pressure.
ScienceA Genetic Polymorphism in the Renin Gene of Dahl Rats Cosegregates with Blood Pressure
295 Citations1989John P. Rapp, Sue-May Wang +1 more
It can be definitively concluded that in the rat the renin gene is, or is closely linked to, one of the genes regulating blood pressure.
BMJEvidence for HL-A-linked genes in "juvenile" diabetes mellitus.
285 Citations1975A G Cudworth, J. C. Woodrow
HL-A typing of 150 patients who had developed diabetes mellitus by the age of 30 years showed a significant association with HL-A 8 and W 15, which appears to be most consistent with the presence of a gene or genes pre-disposing to this type of diabetes at a locus closely linked to the HL- A chromosomal loci.
Journal of Clinical Investigationalpha 1-Antitrypsin: molecular pathology, leukocytes, and tissue damage.
272 Citations1986Robin W. Carrell
HypertensionHypertension prevalence and the status of awareness, treatment, and control in the United States. Final report of the Subcommittee on Definition and Prevalence of the 1984 Joint National Committee.
271 Citations1985
Data from the 1976-1980 National Health and Nutrition Examination Survey (NHANES II) allow for a revised estimate of the prevalence of high blood pressure in the United States and confirm the tendency for the prevalence to increase with age in the U.S. population.
Annals of Human GeneticsThe generalized sib pair IBD distribution: its use in the detection of linkage
242 Citations1978Brian K. Suarez, John P. Rice +1 more
It is shown that the distribution of IBD scores depends only on the additive and dominance variances and the population prevalence of the disorder.
The EMBO JournalHigh blood pressure in transgenic mice carrying the rat angiotensinogen gene.
203 Citations1992Shoji Kimura, John J. Mullins +8 more
The data indicate that overexpression of the angiotensinogen gene in liver and brain leads to the development of hypertension in transgenic mice, and the TGM(rAOGEN)123 constitutes a high ang Elliotensin II type of hypertension and may provide a new experimental animal model to study the kinetics and function of the renin angiotENSin system.
Cardiovascular ResearchKinetics of the human renin and human substrate reaction
188 Citations1971A. B. Gould, Daniel J. Green
The Michaelis constant for the hydrolysis of human renin substrate byhuman renin is 0·931 n-mole/ml, which means substrate concentration in normal serum occurs at a very critical level.
Nucleic Acids ResearchDirect detection and automated sequencing of individual alleles after electrophoretic strand separation: identification of a common nonsense mutation in exon 9 of the human lipoprotein lipase gene
185 Citations1990Akira Hata, Margaret Robertson +2 more
It is shown that mobility shifts of single-stranded DNA electrophoresed under nondenaturing conditions can be used not only to detect variants, but also to separate and sequence directly individual alleles.
Nature GeneticsCosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt–sensitive rats
164 Citations1992Yilun Deng, John P. Rapp
It is concluded that certain alleles at the GCA and ACE loci (or at loci closely linked to them) have a significant genetic impact on blood pressure response to high salt in specific rat strains.
Journal of Clinical InvestigationCosegregation of the renin allele of the spontaneously hypertensive rat with an increase in blood pressure.
154 Citations1990Theodore W. Kurtz, L Simonet +4 more
To the extent that the SHR provides a suitable model of "nonmodulating" hypertension, these findings raise the possibility that a structural alteration in the renin gene, or a closely linked gene, may be a pathogenetic determinant of increased blood pressure in one of the most common forms of essential hypertension in humans.
JAMAFamilial Dyslipidemic Hypertension
149 Citations1988Roger R. Williams
It is concluded that familial dyslipidemic hypertension may be a specific syndrome with lipid abnormalities more severe than blood pressure elevations, probably familial combined hyperlipidemia.
PubMedThe power of identity-by-state methods for linkage analysis.
147 Citations1990D. Timothy Bishop, John Williamson
This work extends the affected-sib-pair method to more distant genetic relationships and examines the power of identity-by-state methods for mapping when marker information is only available on pairs of affected relatives.
Genetic EpidemiologyThe information contained in multiple sibling pairs
143 Citations1984Susan E. Hodge, D. C. Rao
This study examines how much independent information is obtained when all possible pairs are used to evaluate the sharing of genes identical by descent, and a logarithmic measure of information, Σpilog2pi, is used.
Proceedings of the National Academy of SciencesGeneration of transgenic mice with elevated blood pressure by introduction of the rat renin and angiotensinogen genes.
143 Citations1990Hiroaki Ohkubo, Hideshi Kawakami +8 more
Results indicate that the combined action of the exogenous rat renin and angiotensinogen is responsible and necessary for elevation of blood pressure in the hypertensive transgenic mice.
Journal of Biological ChemistryStructure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter.
135 Citations1990Akiyoshi Fukamizu, Shigeru Takahashi +5 more
Analysis of deletion mutants demonstrated that the 76-base pairs region from -32 to +44 containing the TATA box and first exon is the minimal promoter, whose activity is as high as that of the SV40 enhancer-promoter.
DNAStructure of Human Angiotensinogen Gene
133 Citations1989Isabelle Gaillard, Éric Clauser +1 more
The angiotensinogen gene shows identical organization with the alpha 1-antitrypsin gene, but is different from the antithrombin III gene, which may be implicated in the interaction with the hormone receptor complexes.
Human GeneticsSib pair linkage analysis of renin gene haplotypes in human essential hypertension
118 Citations1992Xavier Jeunemaitre, Brigitte Rigat +4 more
The sib pair analysis suggests that the renin gene does not have a frequent role in the pathogenesis of essential hypertension; further more powerful linkage studies or other approaches will be needed to detect contributions at the renIn locus to the heritability of essential pulmonary hypertension.
American Journal of Medical GeneticsA comparison of three affected‐sib‐pair scoring methods to detect HLA‐linked disease susceptibility genes
102 Citations1984Brian K. Suarez, Paul Van Eerdewegh +1 more
Two widely used affected-sib-pair scoring procedures are compared with a new method for their relative efficiency in detecting the presence of an HLA-linked disease susceptibility gene and the new procedure appears to outperform the Green and Woodrow method and the "all-possible-pairs" method.
American Journal of Physiology-Heart and Circulatory PhysiologyComparison of fast and slow pressor effects of angiotensin II in the conscious rat
96 Citations1981AR Brown, J. Casals‐Stenzel +3 more
The slow pressure effect of ANG II develops at a lower and more nearly physiological plasma concentration of the peptide than do the direct pressor effect and the effects on drinking, eating, and urinary sodium excretion.
HypertensionSimilar frequencies of renin gene restriction fragment length polymorphisms in hypertensive and normotensive subjects.
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No association between renin gene polymorphisms and essential hypertension was demonstrated in the present study and the difference was not statistically significant.
The Journal of Clinical Endocrinology & MetabolismEffects of Oral Contraceptive Therapy on the Renin-Angiotensin System
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It is demonstrated that the estrogen-induced rises in plasma renin substrate and renin activity during contraceptive therapy result in high circulating levels of angiotensin II, and confirmatory evidence for the concept that the concomitant suppression of renin secretion i...
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83 Citations1989Éric Clauser, Isabelle Gaillard +2 more
A review of the literature concerning the new aspects of angiotensinogen using molecular biological tools and its regulation together with the characterization of the human angiotENSinogen gene is presented.
HypertensionRole of angiotensinogen in blood pressure homeostasis.
82 Citations1982J. Gardes, J Bouhnik +3 more
It is suggested that angiotensinogen participates in the regulation of blood pressure in normotensive rats, even in the sodium-replete state.
The Journal of Steroid Biochemistry and Molecular BiologySexual dimorphism of blood pressure: Possible role of the renin-angiotensin system
67 Citations1991Jürgen Bachmann, M. Feldmer +3 more
It is demonstrated that the gonadal steroids testosterone and estrogen have important effects on the gene regulation of the renin-angiotensin system, which may contribute to the sexual dimorphism in blood pressure control.
HypertensionBrain and liver angiotensinogen messenger RNA in genetic hypertensive and normotensive rats.
57 Citations1991Brandon G. Yongue, Jesús A. Angulo +2 more
Results are consistent with the possibility that enhanced elaboration of the angiotensin prohormone in the brain contributes, in part, to the hypertension or the elevated salt appetite of the spontaneously hypertensive rat.
Annals of Human GeneticsA test statistic for the affected‐sib‐set method
49 Citations1986Kenneth Lange
Generalizations of the affected‐sib‐pair method are discussed, which make it a more powerful technique for detecting departures from independent segregation of disease and marker phenotypes.
American Journal of Physiology-Renal PhysiologyAltered sodium regulation of renal angiotensinogen mRNA in the spontaneously hypertensive rat
49 Citations1989Richard E. Pratt, Wenbo Zou +3 more
The SHR exhibits an alteration in the sodium regulation of intrarenal angiotensinogen mRNA expression, which may have implications in the renal physiology of these animals.
Nucleic Acids ResearchDinucleotide repeat polymorphism in the human angiotensinogen gene
44 Citations1991Yuri Kotelevtsev, Éric Clauser +2 more
PCR products were heat denatured in 95% formamide, resolved on 5% sequencing gels, and autoradiographed on Amersham MP film.
Advances in human geneticsInvestigation of Genetic Linkage in Human Families
44 Citations1987R. White, Jean-Marc Lalouel
Investigators in human genetics have relied on family studies to identify genetic traits, and the analysis of clusters of clinical symptoms in families has led to the identification of an impressive array of disease entities.
The American Journal of MedicineLow angiotensinogen levels are related to the severity and liver dysfunction of congestive heart failure: implications for renin measurements
35 Citations1991Jean‐François Arnal, Paulette Cudek +4 more
Low levels of plasma renin substrate can be considered as an indirect index of the severity of heart failure that reflects both the high level of circulating active renin and the decrease in hepatic protein output.
EndocrinologyEffects of Estrogen Treatment on Plasma Renin Parameters in the Rat
28 Citations1973Joël Ménard, Kevin Catt
The most notable result of these experiments was the rapid onset of the estrogen—induced rise in circulating renin substrate, which was significantly elevated as early as 6 hr after a single injection of estradiol.
PubMed[Recent advances in the clinical study of the renin system. Reference values and conditions of validity].
27 Citations1989Plouin Pf, Gilles Châtellier +3 more
Plasma renin activity, angiotensinogen, active renin and aldosterone concentrations and, 1 hour after addition of trypsin 1 mg per ml of plasma at -4 degrees C, prorenin and total renin concentrations were measured in 49 normotensive volunteers.
Clinical and Experimental Hypertension Part A Theory and PracticeThe Application of Molecular Genetics to the Study of Familial Arterial Hypertension
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Several strategies can be used for the genetic study of arterial hypertension: linkage studies in informative families, population association studies, analysis of subjects with contrasted predisposition to high blood pressure, affected sib-pair method, and so on.