Ignite Creation Date:
2024-05-05 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005462
Status:
COMPLETED
Last Update Posted:
2016-07-12
First Post:
2000-05-25
Brief Title:
Genetics of Atherosclerosis in Mexican Americans
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:
2008-07
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 identify individual genes that contribute to variation in susceptibility to coronary heart disease CHD in Mexican Americans The program project grant supports the San Antonio Family Heart Study the first comprehensive genetic epidemiological study of atherosclerosis and its correlates in Mexican Americans
Detailed Description:
DESIGN NARRATIVE
The study which began in 1991 focuses on genes that influence the lipoprotein profile in members of randomly ascertained Mexican-American families with particular emphasis on genetic effects on reverse cholesterol transport An overall objective is to investigate the pleiotropic effects of these lipoprotein genes and their interactions with genes that affect non-insulin dependent diabetes mellitus NIDDM antecedents and body fat distribution The interactions of lipoprotein genes with sex hormonal status and with environmental risk factors such as diet exercise and smoking are investigated Genetic effects on standard lipoprotein variables are examined eg plasma concentrations of lipoproteins and apolipoproteins Several novel lipoprotein phenotypes also are analyzed eg amounts of esterified and unesterified cholesterol and of specific apolipoproteins in lipoprotein subclasses Molecular biochemical and statistical genetic approaches are used to detect localize and characterize genes that influence quantitative phenotypes associated with lipoproteins NIDDM and obesity and to quantify the effects of known candidate loci on these phenotypes
The study was renewed in 1997 The subprojects as described in the summary statement are as follows
In Project 1 gene mapping is performed on genes that influence quantitative phenotypes related to the development of atherosclerosis in Mexican American families in the San Antonio Family Heart Study A genomic search using a 10 centimorgan map of 3 91 short tandem report markers distributed throughout the genome is used to determine the chromosomal location of six major genes influencing HDL cholesterol LDL cholesterol apo A1 apob SHBC and DHEAS Evidence for major gene effects is sought for lipoprotein phenotypes for which no major genes have yet been detected Genetic effects on carotid and fibrinolysis phenotypes are quantified using data from a recall of 750 family members Full pedigree variance component analysis as well as penetrance-based methods are used in a genomic search to determine the chromosomal locations of genes that influence these phenotypes To improve genetic models strengthen evidence for linkage and reduce the number of false positives GxE interactions and pleiotropic and epistatic effects of major genes are quantified
In Project 2 a genome-wide search is carried out to localize genes that contribute to quantitative variation in traits related to atherosclerosis NIDDM and obesity The first primary task is the genotyping of some 1400 pedigree members for 391 short tandem repeat STR markers using semi-automated fluorescence based genotyping on an ABI automatic sequencer When statistical evidence of linkage has been evaluated in Projects 1 and 3 and confirmed additional STRs will be typed in the region to further localize the gene The initial map will have a 10 centimorgan resolution Multipoint linkage analysis and gametic disequilibrium analysis will be used to further localize the region containing the gene of interest The human gene map will then be consulted to identify candidate genes in the region and these genes will be subjected to a more detailed molecular analysis to identify structural or functional differences that underlie the observed allelic effects
In Project 3 genetic determinants of NIDDM and obesity are determined and the effects of these genes are specified on lipoproteins carotid wall thickness and other phenotypes pertaining to cardiovascular risk
Core A Field and Clinical Operations has five aims The first is to reexamine 750 of the original study participants near the sixth anniversary of their baseline exam The second is to update demographic information medical history physical activity and dietary habits The third aim is to perform an oral glucose tolerance test with insulin measurement and to obtain fasting blood specimens for other projects and labs The fourth is to perform B-mode ultrasonography exams of the internal carotid artery The fifth is to construct a computerized data file containing these data
Core B Computing and Data Management provides database management for genotypicphenotypic data for clinical and interview data and for pedigrees based on these data
Core C Clinical Phenotypes and Resources performs analyses to measure LDL particle sizes in the frozen samples from the original 1588 samples measures LPA concentrations and performs apoa phenotyping in the recall samples measures plasma lipids and HDL cholesterol in the recall samples and contracts for measurement of fibrinolytic endpoints in the recall sample
Core D is the Administation Core
The study which began in 1991 focuses on genes that influence the lipoprotein profile in members of randomly ascertained Mexican-American families with particular emphasis on genetic effects on reverse cholesterol transport An overall objective is to investigate the pleiotropic effects of these lipoprotein genes and their interactions with genes that affect non-insulin dependent diabetes mellitus NIDDM antecedents and body fat distribution The interactions of lipoprotein genes with sex hormonal status and with environmental risk factors such as diet exercise and smoking are investigated Genetic effects on standard lipoprotein variables are examined eg plasma concentrations of lipoproteins and apolipoproteins Several novel lipoprotein phenotypes also are analyzed eg amounts of esterified and unesterified cholesterol and of specific apolipoproteins in lipoprotein subclasses Molecular biochemical and statistical genetic approaches are used to detect localize and characterize genes that influence quantitative phenotypes associated with lipoproteins NIDDM and obesity and to quantify the effects of known candidate loci on these phenotypes
The study was renewed in 1997 The subprojects as described in the summary statement are as follows
In Project 1 gene mapping is performed on genes that influence quantitative phenotypes related to the development of atherosclerosis in Mexican American families in the San Antonio Family Heart Study A genomic search using a 10 centimorgan map of 3 91 short tandem report markers distributed throughout the genome is used to determine the chromosomal location of six major genes influencing HDL cholesterol LDL cholesterol apo A1 apob SHBC and DHEAS Evidence for major gene effects is sought for lipoprotein phenotypes for which no major genes have yet been detected Genetic effects on carotid and fibrinolysis phenotypes are quantified using data from a recall of 750 family members Full pedigree variance component analysis as well as penetrance-based methods are used in a genomic search to determine the chromosomal locations of genes that influence these phenotypes To improve genetic models strengthen evidence for linkage and reduce the number of false positives GxE interactions and pleiotropic and epistatic effects of major genes are quantified
In Project 2 a genome-wide search is carried out to localize genes that contribute to quantitative variation in traits related to atherosclerosis NIDDM and obesity The first primary task is the genotyping of some 1400 pedigree members for 391 short tandem repeat STR markers using semi-automated fluorescence based genotyping on an ABI automatic sequencer When statistical evidence of linkage has been evaluated in Projects 1 and 3 and confirmed additional STRs will be typed in the region to further localize the gene The initial map will have a 10 centimorgan resolution Multipoint linkage analysis and gametic disequilibrium analysis will be used to further localize the region containing the gene of interest The human gene map will then be consulted to identify candidate genes in the region and these genes will be subjected to a more detailed molecular analysis to identify structural or functional differences that underlie the observed allelic effects
In Project 3 genetic determinants of NIDDM and obesity are determined and the effects of these genes are specified on lipoproteins carotid wall thickness and other phenotypes pertaining to cardiovascular risk
Core A Field and Clinical Operations has five aims The first is to reexamine 750 of the original study participants near the sixth anniversary of their baseline exam The second is to update demographic information medical history physical activity and dietary habits The third aim is to perform an oral glucose tolerance test with insulin measurement and to obtain fasting blood specimens for other projects and labs The fourth is to perform B-mode ultrasonography exams of the internal carotid artery The fifth is to construct a computerized data file containing these data
Core B Computing and Data Management provides database management for genotypicphenotypic data for clinical and interview data and for pedigrees based on these data
Core C Clinical Phenotypes and Resources performs analyses to measure LDL particle sizes in the frozen samples from the original 1588 samples measures LPA concentrations and performs apoa phenotyping in the recall samples measures plasma lipids and HDL cholesterol in the recall samples and contracts for measurement of fibrinolytic endpoints in the recall sample
Core D is the Administation Core
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 |
|---|---|---|---|
| P01HL045522-14 | NIH | None | httpsreporternihgovquickSearchP01HL045522-14 |