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

February 17, 2004
March 18, 2013
September 2003
August 2008   (final data collection date for primary outcome measure)
cardiovascular disease [ Time Frame: 1990-2006 ] [ Designated as safety issue: No ]
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Complete list of historical versions of study NCT00078052 on ClinicalTrials.gov Archive Site
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Genetic Markers of Coronary Heart Disease in Type 2 Diabetes
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To investigate genetic markers of coronary heart disease in type 2 diabetes.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
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Retention:   Samples With DNA
Description:

Plasma and buffy coat

Non-Probability Sample

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

  • Cardiovascular Diseases
  • Coronary Disease
  • Diabetes Mellitus, Non-insulin Dependent
  • Diabetes Mellitus
  • Heart Diseases
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Ma X, Bacci S, Mlynarski W, Gottardo L, Soccio T, Menzaghi C, Iori E, Lager RA, Shroff AR, Gervino EV, Nesto RW, Johnstone MT, Abumrad NA, Avogaro A, Trischitta V, Doria A. A common haplotype at the CD36 locus is associated with high free fatty acid levels and increased cardiovascular risk in Caucasians. Hum Mol Genet. 2004 Oct 1;13(19):2197-205. Epub 2004 Jul 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
120000
August 2008
August 2008   (final data collection date for primary outcome measure)

no history of CVD or cancer at baseline

Both
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No
Contact information is only displayed when the study is recruiting subjects
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NCT00078052
1236, 5R01HL071981-04
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Frank B. Hu, Harvard School of Public Health
Harvard School of Public Health
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Frank Hu Harvard School of Public Health
Harvard School of Public Health
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP