Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00063492 |
| Other study ID # |
1215 |
| Secondary ID |
R01HL070048 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
June 30, 2003 |
| Last updated |
July 23, 2013 |
| Start date |
January 2003 |
| Est. completion date |
December 2007 |
Study information
| Verified date |
July 2013 |
| Source |
University of Utah |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Federal Government |
| Study type |
Observational
|
Clinical Trial Summary
To determine the role of the angiotensinogen gene in human hypertension.
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.
