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Angiotensinogen Gene and Human Hypertension

Primary Purpose

Cardiovascular Diseases, Heart Diseases, Hypertension

Status
Completed
Phase
Locations
Study Type
Observational
Intervention
Sponsored by
University of Utah
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an observational trial for Cardiovascular Diseases

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

No eligibility criteria

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Secondary Outcome Measures

    Full Information

    First Posted
    June 30, 2003
    Last Updated
    July 23, 2013
    Sponsor
    University of Utah
    Collaborators
    National Heart, Lung, and Blood Institute (NHLBI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00063492
    Brief Title
    Angiotensinogen Gene and Human Hypertension
    Study Type
    Observational

    2. Study Status

    Record Verification Date
    July 2013
    Overall Recruitment Status
    Completed
    Study Start Date
    January 2003 (undefined)
    Primary Completion Date
    December 2007 (Actual)
    Study Completion Date
    December 2007 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    University of Utah
    Collaborators
    National Heart, Lung, and Blood Institute (NHLBI)

    4. Oversight

    5. Study Description

    Brief Summary
    To determine the role of the angiotensinogen gene in human hypertension.
    Detailed Description
    BACKGROUND: 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. DESIGN NARRATIVE: 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cardiovascular Diseases, Heart Diseases, Hypertension

    7. Study Design

    10. Eligibility

    Sex
    All
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    No eligibility criteria
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Lynn Jorde
    Organizational Affiliation
    University of Utah

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    15889130
    Citation
    Nakajima T, Wooding S, Satta Y, Jinnai N, Goto S, Hayasaka I, Saitou N, Guan-Jun J, Tokunaga K, Jorde LB, Emi M, Inoue I. Evidence for natural selection in the HAVCR1 gene: high degree of amino-acid variability in the mucin domain of human HAVCR1 protein. Genes Immun. 2005 Aug;6(5):398-406. doi: 10.1038/sj.gene.6364215.
    Results Reference
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    Angiotensinogen Gene and Human Hypertension

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