Genetic Markers of Coronary Heart Disease in Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Frank B. Hu, Harvard School of Public Health
ClinicalTrials.gov Identifier:
NCT00078052
First received: February 17, 2004
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

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


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

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective

Resource links provided by NLM:


Further study details as provided by Harvard School of Public Health:

Primary Outcome Measures:
  • cardiovascular disease [ Time Frame: 1990-2006 ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Plasma and buffy coat


Enrollment: 120000
Study Start Date: September 2003
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Nurses' Health Study and Health Professionals' Follow-up Study

Criteria

no history of CVD or cancer at baseline

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00078052

Sponsors and Collaborators
Harvard School of Public Health
Investigators
Principal Investigator: Frank Hu Harvard School of Public Health
  More Information

Publications:
Responsible Party: Frank B. Hu, Professor, Harvard School of Public Health
ClinicalTrials.gov Identifier: NCT00078052     History of Changes
Other Study ID Numbers: 1236, 5R01HL071981-04
Study First Received: February 17, 2004
Last Updated: March 18, 2013
Health Authority: United States: Federal Government

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

ClinicalTrials.gov processed this record on July 24, 2014