Ignite Creation Date:
2024-05-05 @ 11:31 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00064545
Status:
COMPLETED
Last Update Posted:
2012-12-13
First Post:
2003-07-08
Brief Title:
Gene-by-Smoking Interactions and Risk of Atherosclerosis - Ancillary to ARIC
Sponsor:
University of North Carolina Chapel Hill
Organization:
University of North Carolina Chapel Hill
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 evaluate common genetic variations that in combination with exposure to tobacco smoke may modify the risk of atherosclerosis
Detailed Description:
BACKGROUND
While cigarette smoking is a well-established and potent risk factor for atherosclerotic vascular disease individual susceptibility to smoking varies considerably suggesting modifiers such as genomic variation Several key enzymes involved in the activation and detoxification of mutagenic tobacco smoke compounds oxidative stress and DNA damage are expressed in the tissues of the heart and vasculature and represent mechanistic pathways for tobacco-induced pathology Many of these enzymes have common polymorphisms greater than or equal too 10 prevalence in the population with known functional effects Although restricted to a few enzymes and hampered by shortcomings in design a small number of studies have suggested that enzymatic activation and detoxification of tobacco smoke modifies the risk of certain cardiovascular outcomes associated with cigarette smoking
DESIGN NARRATIVE
The genetic epidemiology study will evaluate common genetic polymorphisms that in combination with exposure to tobacco smoke may modify the risk of atherosclerosis and its clinical sequelae An average of six polymorphisms selected on the basis of their prevalence and functional significance expression in relevant tissues evaluation in previous studies and biologic plausibility within 19 genes involved in activation detoxification oxidative stress and DNA repair pathways will be evaluated as an ancillary study to the Atherosclerosis Risk in Communities ARIC study In this well-characterized bi-ethnic cohort of 15792 men and women under active follow-up since 1987-89 completeness of follow-up 96 five endpoints quantifying subclinical atherosclerosis and validated clinical atherosclerotic events will be studied in case-cohortcase-control mode incident coronary heart disease carotid atherosclerosis peripheral arterial disease incident stroke and MRI-detected cerebral infarcts The study is well designed to study how DNA sequence polymorphisms can promote or inhibit the atherogenic effects of smoking and the risk of clinical events and to contribute new knowledge on the role of genetic variation in the response to environmental insults and toxicants
A case-cohort or case-control approach will be taken using data from the Atherosclerosis Risk in Communities ARIC study Approximately 20 polymorphisms will be examined in relation to five cardiovascular disease CVD endpoints The polymorphisms to be examined are classified as variants of either a Phase I activation enzymes b Phase II detoxification enzymes c oxidative stress enzymes or d DNA repair enzymes The CVD endpoints include incident coronary heart disease CHD cases n1101 incident stroke cases n323 prevalent peripheral artery disease PAD n237 cases carotid atherosclerosis determined by MRI n504 cases and cerebral infarcts n237cases Controls will consist of 1062 controls selected at visit 1 and 237 visit-3 controls for the cerebral infarct cases The statistical approach will be based on the proportional hazards regression for incident CHD and stroke endpoints and logistic regression for the other CVD outcomes Both additive and multiplicative forms of interaction will be tested
While cigarette smoking is a well-established and potent risk factor for atherosclerotic vascular disease individual susceptibility to smoking varies considerably suggesting modifiers such as genomic variation Several key enzymes involved in the activation and detoxification of mutagenic tobacco smoke compounds oxidative stress and DNA damage are expressed in the tissues of the heart and vasculature and represent mechanistic pathways for tobacco-induced pathology Many of these enzymes have common polymorphisms greater than or equal too 10 prevalence in the population with known functional effects Although restricted to a few enzymes and hampered by shortcomings in design a small number of studies have suggested that enzymatic activation and detoxification of tobacco smoke modifies the risk of certain cardiovascular outcomes associated with cigarette smoking
DESIGN NARRATIVE
The genetic epidemiology study will evaluate common genetic polymorphisms that in combination with exposure to tobacco smoke may modify the risk of atherosclerosis and its clinical sequelae An average of six polymorphisms selected on the basis of their prevalence and functional significance expression in relevant tissues evaluation in previous studies and biologic plausibility within 19 genes involved in activation detoxification oxidative stress and DNA repair pathways will be evaluated as an ancillary study to the Atherosclerosis Risk in Communities ARIC study In this well-characterized bi-ethnic cohort of 15792 men and women under active follow-up since 1987-89 completeness of follow-up 96 five endpoints quantifying subclinical atherosclerosis and validated clinical atherosclerotic events will be studied in case-cohortcase-control mode incident coronary heart disease carotid atherosclerosis peripheral arterial disease incident stroke and MRI-detected cerebral infarcts The study is well designed to study how DNA sequence polymorphisms can promote or inhibit the atherogenic effects of smoking and the risk of clinical events and to contribute new knowledge on the role of genetic variation in the response to environmental insults and toxicants
A case-cohort or case-control approach will be taken using data from the Atherosclerosis Risk in Communities ARIC study Approximately 20 polymorphisms will be examined in relation to five cardiovascular disease CVD endpoints The polymorphisms to be examined are classified as variants of either a Phase I activation enzymes b Phase II detoxification enzymes c oxidative stress enzymes or d DNA repair enzymes The CVD endpoints include incident coronary heart disease CHD cases n1101 incident stroke cases n323 prevalent peripheral artery disease PAD n237 cases carotid atherosclerosis determined by MRI n504 cases and cerebral infarcts n237cases Controls will consist of 1062 controls selected at visit 1 and 237 visit-3 controls for the cerebral infarct cases The statistical approach will be based on the proportional hazards regression for incident CHD and stroke endpoints and logistic regression for the other CVD outcomes Both additive and multiplicative forms of interaction will be tested
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 |
|---|---|---|---|
| 5R01HL074377 | NIH | None | httpsreporternihgovquickSearch5R01HL074377 |