Ignite Creation Date:
2024-05-05 @ 11:31 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00064558
Status:
COMPLETED
Last Update Posted:
2022-07-21
First Post:
2003-07-08
Brief Title:
Genetic Determinants of Sudden Cardiac Death
Sponsor:
Brigham and Womens Hospital
Organization:
Brigham and Womens Hospital
Study Overview
Official Title:
Genetic Determinants of Sudden Cardiac Death
Status:
COMPLETED
Status Verified Date:
2022-07
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 evaluate whether genetic variation in selected candidate genes is associated with risk of sudden cardiac death in the general population
Detailed Description:
BACKGROUND Sudden cardiac death SCD affects 400000 individuals each year in the US alone Over half have no evidence of heart disease prior to death and our ability to identify those at risk and therefore prevent SCD is poor Mutations in cardiac ion channel genes including SCN5A KCNQ1 KCNH2 KCNE1 KCNE2 and RyR2 have been implicated in monogenic traits with high risk of SCD such as the long-QT Brugada sudden infant death syndrome SIDS and catecholaminergic polymorphic ventricular tachycardia Alterations in ion channel function can result in life-threatening ventricular arrhythmias in diverse disease states Therefore sequence variants in these genes that alter function or transcription of these ion channels may confer a predisposition to ventricular arrhythmia and SCD in broader populations
DESIGN NARRATIVE This research program proposes to determine if sequence variants in the above and other candidate genes are associated with an increased risk of SCD in apparently-healthy populations Cases of SCD will be assembled from 5 NIH-funded prospective cohorts with a total of 106314 individuals with existent blood samples All cohorts are exceptionally well-characterized with respect to environmental exposures and have collected medical records on cardiovascular endpoints We will characterize all coding sequence variation and selected non-coding sequence variation among 100 cases and controls from these cohorts for the 6 genes We will then employ a nested case-control design and conditional logistic regression to test for associations between haplotypes haplotype tag SNPs in both coding and non-coding regions of candidate genes and SCD risk We will also test directly for associations between single loci that may have functional significance and SCD risk An estimated 600 cases of well-documented SCD will be confirmed over the first 3 years of the grant period and these cases will be matched on age sex ethnicity and geographic location to two control subjects from the same cohort In addition based upon known sex difference in the phenotypic expression of the candidate genes in the primary arrhythmic disorders we will specifically examine sex difference in the risk of SCD associated with sequence variation in these genes The findings generated will have substantial implications for our understanding of the SCD syndrome and risk stratification in the general population
DESIGN NARRATIVE This research program proposes to determine if sequence variants in the above and other candidate genes are associated with an increased risk of SCD in apparently-healthy populations Cases of SCD will be assembled from 5 NIH-funded prospective cohorts with a total of 106314 individuals with existent blood samples All cohorts are exceptionally well-characterized with respect to environmental exposures and have collected medical records on cardiovascular endpoints We will characterize all coding sequence variation and selected non-coding sequence variation among 100 cases and controls from these cohorts for the 6 genes We will then employ a nested case-control design and conditional logistic regression to test for associations between haplotypes haplotype tag SNPs in both coding and non-coding regions of candidate genes and SCD risk We will also test directly for associations between single loci that may have functional significance and SCD risk An estimated 600 cases of well-documented SCD will be confirmed over the first 3 years of the grant period and these cases will be matched on age sex ethnicity and geographic location to two control subjects from the same cohort In addition based upon known sex difference in the phenotypic expression of the candidate genes in the primary arrhythmic disorders we will specifically examine sex difference in the risk of SCD associated with sequence variation in these genes The findings generated will have substantial implications for our understanding of the SCD syndrome and risk stratification in the general population
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 |
|---|---|---|---|
| R01HL068070 | NIH | None | httpsreporternihgovquickSearchR01HL068070 |