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Sponsored by: |
National Heart, Lung, and Blood Institute (NHLBI) |
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Information provided by: | National Heart, Lung, and Blood Institute (NHLBI) |
ClinicalTrials.gov Identifier: | NCT00078052 |
To investigate genetic markers of coronary heart disease in type 2 diabetes.
Condition | Phase |
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Cardiovascular Diseases Coronary Disease Diabetes Mellitus, Non-Insulin Dependent Diabetes Mellitus Heart Diseases |
N/A |
Study Type: | Observational |
Study Start Date: | September 2003 |
Study Completion Date: | August 2008 |
Primary Completion Date: | August 2008 (Final data collection date for primary outcome measure) |
BACKGROUND:
Coronary heart disease (CHD), as the leading cause of death in the United States, is of significant public health concern. Despite the knowledge that atherosclerosis is the underlying cause of CHD, the recognition that both genetic and environmental factors contribute to the occurrence of disease, and the identification of a large number of genetic and environmental factors that have been found to be associated with disease risk, the etiology of atherosclerosis with the later development CHD continues to be not very well understood.
DESIGN NARRATIVE:
The nested case-control study will determine whether variability in 20 genes belonging to endothelial and inflammatory dysfunction pathways is related to the risk of coronary heart disease (CHD) among men and women diagnosed with type 2 diabetes in two large ongoing prospective studies, the Nurses' Health Study (NHS) and Health Professionals' Follow-up Study (HPFS). This will be accomplished by combining two complementary approaches that are made possible by the recent advances in knowledge of the human genome and high-throughput genotyping technologies. The investigators will directly target functional variants in the coding regions of the candidate genes and also investigate the association between CHD and ancestral haplotypes at each locus.
The specific aims are: 1. To identify novel variants in 10 candidate genes of the inflammatory, and endothelial dysfunction pathways that have not been systematically screened for polymorphisms by targeted resequencing; 2. To assess the relationship between functional variants in 20 candidate genes in the inflammatory and endothelial dysfunction pathways and risk of CHD among subjects with diabetes of the NHS and HPFS cohorts; 3. To identify the subset of polymorphisms that best capture the overall genetic variability at each locus (haplotype tagging single nucleotide polymorphisms (SNPs) or htSNPs) and investigate the association between CHD risk and the haplotypes defined by these htSNPs; 4. To examine individual SNPs as well as haplotypes in relation to biochemical markers of inflammation and endothelial activation such as CRP, ICAM-1, VCAM-1, E-selectin, and TNF-a in diabetic individuals; and 5. To examine gene-environment interactions in relation to CHD risk in diabetic subjects. By 2006, an estimated 820 cases of CHD will have been confirmed among diabetic men and women in the blood cohorts. The large size, prospective design, high follow-up rates, detailed and reliable long-term lifestyle and outcome information, and the availability of blood specimens make these cohorts a valuable and unique resource for studying genetic determinants of accelerated atherosclerosis in diabetic patients.
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
No eligibility criteria
Study ID Numbers: | 1236 |
Study First Received: | February 17, 2004 |
Last Updated: | August 20, 2008 |
ClinicalTrials.gov Identifier: | NCT00078052 History of Changes |
Health Authority: | United States: Federal Government |
Arterial Occlusive Diseases Heart Diseases Metabolic Diseases Myocardial Ischemia Diabetes Mellitus Vascular Diseases Endocrine System Diseases Ischemia |
Arteriosclerosis Coronary Disease Diabetes Mellitus, Type 2 Endocrinopathy Glucose Metabolism Disorders Metabolic Disorder Coronary Artery Disease |
Arterial Occlusive Diseases Heart Diseases Metabolic Diseases Myocardial Ischemia Diabetes Mellitus Vascular Diseases Endocrine System Diseases |
Arteriosclerosis Coronary Disease Diabetes Mellitus, Type 2 Cardiovascular Diseases Glucose Metabolism Disorders Coronary Artery Disease |