Ignite Creation Date:
2024-05-05 @ 11:39 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00090441
Status:
COMPLETED
Last Update Posted:
2013-01-04
First Post:
2004-08-26
Brief Title:
Risk Burden of Lipoprotein Metabolic Gene Haplotypes
Sponsor:
Intermountain Health Care Inc
Organization:
Intermountain Health Care Inc
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2012-12
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 role in coronary heart disease CHD of intragenic variation in a network of six genes affecting lipoprotein transport and metabolism
Detailed Description:
BACKGROUND
In recent years a number of candidate genetic variants eg single nucleotide polymorphisms SNPs have been reported to be associated with coronary heart disease CHD However these association studies have suffered from variability and failures of replication This may result in part from selection of marker SNPs in linkage disequilibrium LD with true disease-related SNPs or with other effect-modulating genetic variants Other issues include the play of chance in samples of limited size population stratification artifacts and small effect size for single SNPs A recent discovery is that the genome is organized into largely invariant DNA fragments at the population level characterized by infrequent recombination events interspersed with hotspots of recombination and designated haplotype blocks These haplotype blocks can be determined by creating a dense map of SNPs across the gene of interest and analyzing population level LD A few SNPs then can be chosen that designate tag each haplotype block and used to comprehensively assess disease associations across the entire gene Applying this approach to multiple genes in pathways critical to vascular health and assessing combinations of genes is likely to increase the power to discover genetic associations with CHD risk
DESIGN NARRATIVE
The study will establish high density SNP maps across exons splice regions and 5 and 3 regulatory regions of 6 genes that play key roles in lipoprotein transport and metabolism ABCA1 CETP LCAT HL LPL SRB1 introns will be examined for 2 of the genes CETP LPL By analyzing combinations of haplotype-tagging ht SNPs genetic burden can be scored and correlated with CHD risk at 4 levels 1 biomarker lipidlipoprotein levels 2 anatomic angiographic CHD 3 clinical outcome deathMI and 4 exploratory response to lipid-lowering Testing will be performed in 3 large distinct but complementary Utah populations at primary or secondary risk of premature CHD Testing will occur in 2 stages to establish reproducibility an initial screening phase followed by a confirmation phase for genetic markers and combinations showing promise in a larger independent sample The study will employ novel methods that combine high-throughput SNP discovery and genotyping capability with genetic epidemiological methods to identify the haplotype blocks within and surrounding the genes of interest identify htSNPs and assess disease associations with individual and combinations of htSNPs genetic burden To this the study brings large well characterized databases assembled and followed for up to 9 years which will be further expanded under the current project
In recent years a number of candidate genetic variants eg single nucleotide polymorphisms SNPs have been reported to be associated with coronary heart disease CHD However these association studies have suffered from variability and failures of replication This may result in part from selection of marker SNPs in linkage disequilibrium LD with true disease-related SNPs or with other effect-modulating genetic variants Other issues include the play of chance in samples of limited size population stratification artifacts and small effect size for single SNPs A recent discovery is that the genome is organized into largely invariant DNA fragments at the population level characterized by infrequent recombination events interspersed with hotspots of recombination and designated haplotype blocks These haplotype blocks can be determined by creating a dense map of SNPs across the gene of interest and analyzing population level LD A few SNPs then can be chosen that designate tag each haplotype block and used to comprehensively assess disease associations across the entire gene Applying this approach to multiple genes in pathways critical to vascular health and assessing combinations of genes is likely to increase the power to discover genetic associations with CHD risk
DESIGN NARRATIVE
The study will establish high density SNP maps across exons splice regions and 5 and 3 regulatory regions of 6 genes that play key roles in lipoprotein transport and metabolism ABCA1 CETP LCAT HL LPL SRB1 introns will be examined for 2 of the genes CETP LPL By analyzing combinations of haplotype-tagging ht SNPs genetic burden can be scored and correlated with CHD risk at 4 levels 1 biomarker lipidlipoprotein levels 2 anatomic angiographic CHD 3 clinical outcome deathMI and 4 exploratory response to lipid-lowering Testing will be performed in 3 large distinct but complementary Utah populations at primary or secondary risk of premature CHD Testing will occur in 2 stages to establish reproducibility an initial screening phase followed by a confirmation phase for genetic markers and combinations showing promise in a larger independent sample The study will employ novel methods that combine high-throughput SNP discovery and genotyping capability with genetic epidemiological methods to identify the haplotype blocks within and surrounding the genes of interest identify htSNPs and assess disease associations with individual and combinations of htSNPs genetic burden To this the study brings large well characterized databases assembled and followed for up to 9 years which will be further expanded under the current project
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 5R01HL071878-04 | NIH | None | httpsreporternihgovquickSearch5R01HL071878-04 |