Ignite Creation Date:
2024-05-05 @ 10:23 AM
Last Modification Date:
2024-10-26 @ 9:04 AM
Study NCT ID:
NCT00005268
Status:
COMPLETED
Last Update Posted:
2016-08-08
First Post:
2000-05-25
Brief Title:
Family Blood Pressure Program - GenNet Network
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:
2008-08
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 identify new genetic loci regulating blood pressure in hypertensive rats and in case-controls from relevant human populations The study consists of a four grant network which in turn is part of an NHLBI initiative the Family Blood Pressure Program FBPP consisting of four networks
Detailed Description:
BACKGROUND
Hypertension a complex disease involving the interplay of genetic and environmental factors affects an estimated 50 million Americans and is a major predisposing factor for myocardial infarction vascular disease stroke and renal failure It has been estimated from segregation analysis and twin studies that approximately 45 percent of the interindividual differences in blood pressure are accounted for by genetic differences The identification of the genes whose variants contribute to high blood pressure will have far-reaching effects on our understanding of the pathophysiology of the circulation and may suggest new preventive measures and rational therapeutic approaches
One of the principal advantages of the genetic approach is that it identifies primary molecular defects As a result it will be possible to stratify the general hypertensive population into subgroups based on genotype and intermediate phenotype and thereby evaluate preventive strategies and therapeutic approaches in more homogeneous groups In addition the identification of hypertensive genes also provides the basis for an understanding of the interactions between genes and environmental factors It is very likely that particular environmental variables exert their effects only in the presence of certain genotypes
Until recently the techniques for dissecting the genetic determinants of high blood pressure were not available or were not developed to an extent that would make the Family Blood Pressure Program initiative feasible However several recent advances in technology and analytical methods together with the rapid construction of genetic maps have substantially improved the chances of detecting these genetic factors
The concept for the Family Blood Pressure Program was conceived in the Report of the Expert Panel on Genetic Strategies for Heart Lung and Blood Diseases The initiative was approved by the Arteriosclerosis Hypertension and Lipid Metabolism Advisory Committee AHLMAC in March 1993 The genetic-epidemiological aspects were approved by the Clinical Applications and Prevention Advisory Committee CAPAC in February 1993 The Request for Applications was released in March 1994 Awards were made in September 1995
DESIGN NARRATIVE
The network consists of five centers two field centers a rat genotyping center a human genotyping center with statistical genetics and informatics and a genetic analysis center After genetic loci regulating blood pressure are identified genomic markers are used to study genetic linkage with red blood cell lithium-sodium countertransport hyperkinetic hyperadrenergic state and the renin-angiotensin system in sibships and tested in several Black populations
The well-characterized Tecumseh population was utilized as a first step in determining genetic linkage to hypertension using the quantitative trait locus QTL approach A total of 250 white sibships in the Tecumseh population were examined using 400 anonymous markers and candidate genes Approximately 100 markers that demonstrated linkage were used to examine 250 African-American sibships in Maywood Illinois Fifty refined candidate markers were used to study several extant Black populations in Jamaica and Nigeria as well as individuals in the other two populations A unique feature of the network is the inclusion of a rat genotyping center Crosses of inbred hypertensive and normotensive rats are used to identify genomic regions linked to hypertension The regions are then used to identify homologous human candidate genes in addition to those already selected from previous research
The GenNet Network was renewed in September 2000 to continue studies of hypertension-associated phenotypes in United States whites African Americans Mexican Americans and West Africans and Caribbeans The Family Blood Pressure Program as a whole carried out five specific aims in the renewal period These aims were grouped according to two complementary themes First the investigators created and analyzed a database of blood pressure-related phenotype and genotype data from all FBPP participants Aim 1 Within linked regions they identified allelic variation within positional candidate genes and evaluated the relationship of these polymorphisms with blood pressure levels and hypertension status Aims 2 and 3 Second they used quantitative measures of target organ damage to identify genes that influenced susceptibility to develop hypertensive heart and kidney diseases Aims 4 and 5 In addition to the Program specific aims each network including GenNet carried out its own specific aims alone based on unique aspects of their population and interests and expertise of the investigators In GenNet progress has been made in the identification of single nucleotide polymorphisms SNPs in candidate genes and work was underway to develop rapid genotyping methods in individual and pool samples The search for genes in diverse human populations was complemented by mapping studies in rat strains in which linked regions that overlap with regions showing evidence for linkage in the human studies were selected for positional cloning
In the next phase of the FBPP ending in August 2008 a major emphasis is placed on making the Program a shared resource for hypertension researchers in the United States and throughout the world In Aim 1 the investigators will build maintain and update a publicly available knowledge-base to facilitate research by non-FBPP investigators on the genetics of hypertension its risk factors and its complications In Aim 2 they will use state-of-the-art genetic linkage analysis methods to identify additional linkage regions using subgroups of pedigrees and physiologically relevant combinations of phenotypes that will aid in localizing hypertension genes In Aim 3 they will use a combination of bioinformatics a dense array of SNPs and state-of-the-art data analysis to follow-up regions of interest and identify the underlying hypertension genes The regions to be followed-up include those identified during the current phase of the FBPP and Aim 2 of this renewal phase In Aim 4 they will evaluate the hypertension genes identified in Aim 3 for their association with multiple measures reflecting the cardiovascular and renal complications of hypertension including left ventricular mass and microalbuminuria It is the long-term goal of the FBPP to have the hypertension genetics community develop a comprehensive picture of the genetic architecture of human hypertension including its risk factors complications and response to treatment
Hypertension a complex disease involving the interplay of genetic and environmental factors affects an estimated 50 million Americans and is a major predisposing factor for myocardial infarction vascular disease stroke and renal failure It has been estimated from segregation analysis and twin studies that approximately 45 percent of the interindividual differences in blood pressure are accounted for by genetic differences The identification of the genes whose variants contribute to high blood pressure will have far-reaching effects on our understanding of the pathophysiology of the circulation and may suggest new preventive measures and rational therapeutic approaches
One of the principal advantages of the genetic approach is that it identifies primary molecular defects As a result it will be possible to stratify the general hypertensive population into subgroups based on genotype and intermediate phenotype and thereby evaluate preventive strategies and therapeutic approaches in more homogeneous groups In addition the identification of hypertensive genes also provides the basis for an understanding of the interactions between genes and environmental factors It is very likely that particular environmental variables exert their effects only in the presence of certain genotypes
Until recently the techniques for dissecting the genetic determinants of high blood pressure were not available or were not developed to an extent that would make the Family Blood Pressure Program initiative feasible However several recent advances in technology and analytical methods together with the rapid construction of genetic maps have substantially improved the chances of detecting these genetic factors
The concept for the Family Blood Pressure Program was conceived in the Report of the Expert Panel on Genetic Strategies for Heart Lung and Blood Diseases The initiative was approved by the Arteriosclerosis Hypertension and Lipid Metabolism Advisory Committee AHLMAC in March 1993 The genetic-epidemiological aspects were approved by the Clinical Applications and Prevention Advisory Committee CAPAC in February 1993 The Request for Applications was released in March 1994 Awards were made in September 1995
DESIGN NARRATIVE
The network consists of five centers two field centers a rat genotyping center a human genotyping center with statistical genetics and informatics and a genetic analysis center After genetic loci regulating blood pressure are identified genomic markers are used to study genetic linkage with red blood cell lithium-sodium countertransport hyperkinetic hyperadrenergic state and the renin-angiotensin system in sibships and tested in several Black populations
The well-characterized Tecumseh population was utilized as a first step in determining genetic linkage to hypertension using the quantitative trait locus QTL approach A total of 250 white sibships in the Tecumseh population were examined using 400 anonymous markers and candidate genes Approximately 100 markers that demonstrated linkage were used to examine 250 African-American sibships in Maywood Illinois Fifty refined candidate markers were used to study several extant Black populations in Jamaica and Nigeria as well as individuals in the other two populations A unique feature of the network is the inclusion of a rat genotyping center Crosses of inbred hypertensive and normotensive rats are used to identify genomic regions linked to hypertension The regions are then used to identify homologous human candidate genes in addition to those already selected from previous research
The GenNet Network was renewed in September 2000 to continue studies of hypertension-associated phenotypes in United States whites African Americans Mexican Americans and West Africans and Caribbeans The Family Blood Pressure Program as a whole carried out five specific aims in the renewal period These aims were grouped according to two complementary themes First the investigators created and analyzed a database of blood pressure-related phenotype and genotype data from all FBPP participants Aim 1 Within linked regions they identified allelic variation within positional candidate genes and evaluated the relationship of these polymorphisms with blood pressure levels and hypertension status Aims 2 and 3 Second they used quantitative measures of target organ damage to identify genes that influenced susceptibility to develop hypertensive heart and kidney diseases Aims 4 and 5 In addition to the Program specific aims each network including GenNet carried out its own specific aims alone based on unique aspects of their population and interests and expertise of the investigators In GenNet progress has been made in the identification of single nucleotide polymorphisms SNPs in candidate genes and work was underway to develop rapid genotyping methods in individual and pool samples The search for genes in diverse human populations was complemented by mapping studies in rat strains in which linked regions that overlap with regions showing evidence for linkage in the human studies were selected for positional cloning
In the next phase of the FBPP ending in August 2008 a major emphasis is placed on making the Program a shared resource for hypertension researchers in the United States and throughout the world In Aim 1 the investigators will build maintain and update a publicly available knowledge-base to facilitate research by non-FBPP investigators on the genetics of hypertension its risk factors and its complications In Aim 2 they will use state-of-the-art genetic linkage analysis methods to identify additional linkage regions using subgroups of pedigrees and physiologically relevant combinations of phenotypes that will aid in localizing hypertension genes In Aim 3 they will use a combination of bioinformatics a dense array of SNPs and state-of-the-art data analysis to follow-up regions of interest and identify the underlying hypertension genes The regions to be followed-up include those identified during the current phase of the FBPP and Aim 2 of this renewal phase In Aim 4 they will evaluate the hypertension genes identified in Aim 3 for their association with multiple measures reflecting the cardiovascular and renal complications of hypertension including left ventricular mass and microalbuminuria It is the long-term goal of the FBPP to have the hypertension genetics community develop a comprehensive picture of the genetic architecture of human hypertension including its risk factors complications and response to treatment
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 |
|---|---|---|---|
| 5U01HL054512 | NIH | None | httpsreporternihgovquickSearch5U01HL054512 |