Angiotensinogen Gene and Human Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00063492
Recruitment Status : Completed
First Posted : July 1, 2003
Last Update Posted : July 24, 2013
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:
University of Utah

Brief Summary:
To determine the role of the angiotensinogen gene in human hypertension.

Condition or disease
Cardiovascular Diseases Heart Diseases Hypertension

Detailed Description:


Essential hypertension affects at least 25 percent of American adults, and it is a primary risk factor for heart failure, stroke, and kidney disease. Many, but not all, studies have shown that variants of the angiotensinogen gene (AGT) affect the risk of hypertension, but association studies conducted to date have been compromised by genetic heterogeneity and by the inherent complexity of hypertension as a phenotype.


A comprehensive study of the angiotensinogen (AGT) gene will be conducted in data collected from several large groups of individuals. The investigators will sequence or genotype a 14.4 kb region including AGT in more than 1,600 individuals sampled from populations throughout the world. This will permit them to explore fully the extent of allelic heterogeneity, haplotype variation, and potential for population stratification in the AGT gene. Approximately 600 of these individuals are clinically uncharacterized and will represent a broad range of worldwide human variation. Another 500 subjects are members of 40 Utah pedigrees that are part of the Centre d'Etude du Polymorphisme Humain (CEPH) collection. These unique families have been heavily characterized genetically, and they are now being phenotyped for variables that include anthropometrics, blood chemistries, blood pressure measures, and plasma and urinary angiotensinogen. They will address the issue of genetic heterogeneity by testing associations between multi-SNP AGT haplotypes, angiotensinogen levels, and blood pressure. In addition, linkage disequilibrium patterns will be assessed to determine the density and nature of SNPs best suited for localizing a gene underlying a complex trait. They will address the issue of phenotypic heterogeneity in hypertension by performing extensive SNP typing on a set of 400 hypertensives and 100 normotensives collected by Dr. Gordon Williams. These clinically well-characterized subjects have been tested for their response to infused angiotensin-II under high and low sodium intake. This direct probe provides a hypertension endophenotype that is closer to the function of the AGT gene, yielding a more realistic and informative assessment of the relationship between AGT haplotype variation and hypertension risk. A phylogenetic analysis of AGT sequence variation in the worldwide sample will help to assess population stratification in association studies. In addition, this sample will allow testing the hypothesis that the ancestral T235 AGT allele provided a selective advantage in the sodium-poor environment of sub-Saharan Africa. The results of this analysis may help to explain why African-Americans have elevated rates of hypertension. In summary, the extensive analysis of AGT variation in more than 1,600 subjects will clarify the role of this gene in essential hypertension and will test specific hypotheses about the evolution of AGT.

Study Type : Observational
Study Start Date : January 2003
Actual Primary Completion Date : December 2007
Actual Study Completion Date : December 2007

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
No eligibility criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00063492

Sponsors and Collaborators
University of Utah
National Heart, Lung, and Blood Institute (NHLBI)
OverallOfficial: Lynn Jorde University of Utah