Genetic Markers of Coronary Heart Disease in Type 2 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00078052
Recruitment Status : Completed
First Posted : February 19, 2004
Last Update Posted : March 20, 2013
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Frank B. Hu, Harvard School of Public Health

Brief Summary:
To investigate genetic markers of coronary heart disease in type 2 diabetes.

Condition or disease
Cardiovascular Diseases Coronary Disease Diabetes Mellitus, Non-insulin Dependent Diabetes Mellitus Heart Diseases

Detailed Description:


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.


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.

Study Type : Observational
Actual Enrollment : 120000 participants
Observational Model: Cohort
Time Perspective: Prospective
Study Start Date : September 2003
Actual Primary Completion Date : August 2008
Actual Study Completion Date : August 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Diseases
U.S. FDA Resources

Primary Outcome Measures :
  1. cardiovascular disease [ Time Frame: 1990-2006 ]

Biospecimen Retention:   Samples With DNA
Plasma and buffy coat

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Nurses' Health Study and Health Professionals' Follow-up Study
no history of CVD or cancer at baseline

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00078052

Sponsors and Collaborators
Harvard School of Public Health
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Frank Hu Harvard School of Public Health

Responsible Party: Frank B. Hu, Professor, Harvard School of Public Health Identifier: NCT00078052     History of Changes
Other Study ID Numbers: 1236
5R01HL071981-04 ( U.S. NIH Grant/Contract )
First Posted: February 19, 2004    Key Record Dates
Last Update Posted: March 20, 2013
Last Verified: March 2013

Additional relevant MeSH terms:
Diabetes Mellitus
Cardiovascular Diseases
Heart Diseases
Coronary Disease
Coronary Artery Disease
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Myocardial Ischemia
Vascular Diseases
Arterial Occlusive Diseases