Ignite Creation Date:
2024-05-05 @ 11:30 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00063492
Status:
COMPLETED
Last Update Posted:
2013-07-24
First Post:
2003-06-30
Brief Title:
Angiotensinogen Gene and Human Hypertension
Sponsor:
University of Utah
Organization:
University of Utah
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2013-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 144 kb region including AGT in more than 1600 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 dEtude 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 1600 subjects will clarify the role of this gene in essential hypertension and will test specific hypotheses about the evolution of AGT
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 144 kb region including AGT in more than 1600 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 dEtude 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 1600 subjects will clarify the role of this gene in essential hypertension and will test specific hypotheses about the evolution of AGT
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL070048 | NIH | None | httpsreporternihgovquickSearchR01HL070048 |