Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005387
Status:
COMPLETED
Last Update Posted:
2016-07-12
First Post:
2000-05-25
Brief Title:
Genetics of Hypertension in Blacks
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2008-12
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 investigate the genetic determinants of hypertension in three populations of the African diaspora with a major focus on clarifying the role of genes that code for the renin-angiotensin system RAS
Detailed Description:
BACKGROUND
This community-based study in three geographically distinct populations of West African heritage with contrasting levels of hypertension risk was one of the first comprehensive examinations of the genetics of hypertension in African Americans The study focused on the renin-angiotensin system RAS because it was the only physiological arm of blood pressure control for which candidate genes had been securely linked to the risk of hypertension Polymorphisms at the angiotensinogen locus varied considerably between Blacks and whites The documented Blackwhite differences in the RAS system emphasized the importance of determining whether RAS genes contributed to the excessively high risk of hypertension experienced by African Americans The study generated unique information about the variability of the RAS loci in populations of West African heritage and the contribution of this variability to hypertension risk The data from the study including the DNA specimens also represented a valuable resource for future work on the genetics of hypertension in this important ethnic group
DESIGN NARRATIVE
The primary goals of this study were 1 Determine the extent to which genetic variability of the RAS genes influenced the distribution of blood pressure and of RAS intermediate phenotypes within each population and contrast the results across populations 2 Use family studies within each population to determine the degree-of familial aggregation of blood pressure and of the RAS intermediate phenotypes 3 Use segregation analysis to determine the contribution of major genes to the familial aggregation of blood pressure and of hypertension and determine whether RAS genes cosegregate with hypertension or with RAS intermediate phenotypes 4 Evaluate whether the different prevalence of hypertension in each community reflected differences in their genetic background The study sites included Ibadan Nigeria Kingston Jamaica and Maywood IL At each site genetic and epidemiological data were collected from individuals sampled as follows individuals comprising 100 five- member structured family sets proband spouse two sibs one offspring or half-sib equally ascertained from the highest and lowest quartiles of the blood pressure distribution as defined by an ongoing community-wide survey unrelated singletons also sampled equally from the highest and lowest blood pressure quartiles The following measurements were obtained from all participants Epidemiological variables blood pressure height weight waisthip ratio skinfolds urine sodiumpotassium and sociodemographic variables Intermediate phenotypes Plasma levels of angiotensinogen renin and angiotensin-converting enzyme ACE Genotypes A set of DNA polymorphisms at the four main RAS loci angiotensinogen renin ACE and the angiotensin II-type l receptor
The study was renewed in FY 2000 To further elucidate the environmental pathways the investigators conducted a substudy cross-classifying participants on the major risk determinants ie obesity and sodium intake and they examined gene-environment interactions directly They used a genome scan in linkage analysis to identify new chromosomal regions of interest They also examine two new candidate loci adducin and beta-2 adrenergic receptor and conducted association studies using single nucleotide polymorphisms They used the full range of analytic tools including segregation linkage and cladistic analysis
The study was renewed again in FY 2005 to supplement evidence of hypertension causation on chromosomes 67 and 11 with a new set of dense markers and to search for positional candidate genes for hypertension at the two best regions identify the genes under the linkage peaks find appropriate single nucleotide polymorphisms for a frequency of greater than 10 and conduct associationlinkage disequilibrium mapping replicate these findings in additional case-control studies and assess potential gene-environment interactions
This community-based study in three geographically distinct populations of West African heritage with contrasting levels of hypertension risk was one of the first comprehensive examinations of the genetics of hypertension in African Americans The study focused on the renin-angiotensin system RAS because it was the only physiological arm of blood pressure control for which candidate genes had been securely linked to the risk of hypertension Polymorphisms at the angiotensinogen locus varied considerably between Blacks and whites The documented Blackwhite differences in the RAS system emphasized the importance of determining whether RAS genes contributed to the excessively high risk of hypertension experienced by African Americans The study generated unique information about the variability of the RAS loci in populations of West African heritage and the contribution of this variability to hypertension risk The data from the study including the DNA specimens also represented a valuable resource for future work on the genetics of hypertension in this important ethnic group
DESIGN NARRATIVE
The primary goals of this study were 1 Determine the extent to which genetic variability of the RAS genes influenced the distribution of blood pressure and of RAS intermediate phenotypes within each population and contrast the results across populations 2 Use family studies within each population to determine the degree-of familial aggregation of blood pressure and of the RAS intermediate phenotypes 3 Use segregation analysis to determine the contribution of major genes to the familial aggregation of blood pressure and of hypertension and determine whether RAS genes cosegregate with hypertension or with RAS intermediate phenotypes 4 Evaluate whether the different prevalence of hypertension in each community reflected differences in their genetic background The study sites included Ibadan Nigeria Kingston Jamaica and Maywood IL At each site genetic and epidemiological data were collected from individuals sampled as follows individuals comprising 100 five- member structured family sets proband spouse two sibs one offspring or half-sib equally ascertained from the highest and lowest quartiles of the blood pressure distribution as defined by an ongoing community-wide survey unrelated singletons also sampled equally from the highest and lowest blood pressure quartiles The following measurements were obtained from all participants Epidemiological variables blood pressure height weight waisthip ratio skinfolds urine sodiumpotassium and sociodemographic variables Intermediate phenotypes Plasma levels of angiotensinogen renin and angiotensin-converting enzyme ACE Genotypes A set of DNA polymorphisms at the four main RAS loci angiotensinogen renin ACE and the angiotensin II-type l receptor
The study was renewed in FY 2000 To further elucidate the environmental pathways the investigators conducted a substudy cross-classifying participants on the major risk determinants ie obesity and sodium intake and they examined gene-environment interactions directly They used a genome scan in linkage analysis to identify new chromosomal regions of interest They also examine two new candidate loci adducin and beta-2 adrenergic receptor and conducted association studies using single nucleotide polymorphisms They used the full range of analytic tools including segregation linkage and cladistic analysis
The study was renewed again in FY 2005 to supplement evidence of hypertension causation on chromosomes 67 and 11 with a new set of dense markers and to search for positional candidate genes for hypertension at the two best regions identify the genes under the linkage peaks find appropriate single nucleotide polymorphisms for a frequency of greater than 10 and conduct associationlinkage disequilibrium mapping replicate these findings in additional case-control studies and assess potential gene-environment interactions
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 |
|---|---|---|---|
| R01HL053353 | NIH | None | httpsreporternihgovquickSearchR01HL053353 |