Clinical trial NCT00046605: Inflammation Genomics and Atherosclerosis - Ancillary to CARDIA
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiovascular Diseases
Atherosclerosis
Coronary Arteriosclerosis
Inflammation
Heart Diseases
Thrombosis
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2002-10-01
Enrollment: 3600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Same as eligibility criteria

Brief summary: To examine the associations of common variation in inflammation/thrombosis genes with intermediate quantitative phenotypes and subclinical coronary atherosclerosis in the Coronary Artery Risk Factor Development in Young Adults (CARDIA) Study, a large, bi-racial cohort study.

Detailed description: BACKGROUND:

Atherosclerosis is a major determinant of coronary heart disease and is determined by the interplay of genetic and environmental risk factors. Although atherosclerosis tends to aggregate in families, it does not exhibit classical Mendelian segregation. Thus, the genes that determine an individual's risk of atherosclerosis likely involve multiple sites within genes and interactions between genes, all of which define a genetic risk that is modified by the host environment.

DESIGN NARRATIVE:

The genetic epidemiology study examines the associations of common variation in inflammation/thrombosis genes with intermediate quantitative phenotypes and subclinical coronary atherosclerosis in the Coronary Artery Risk Factor Development in Young Adults (CARDIA) Study, a large, bi-racial cohort study. The set of 25 candidate genes involve pathways (cytokines, chemokines, and their receptors; cellular adhesion molecules; and, coagulation proteins) and include several receptor-ligand pairs. Using cladistic analysis and the resources of the Program in Genomic Applications (PGA), the investigators will identify a limited set of single nucleotide polymorphisms (range 3-10 SNPs per gene) that characterize common haplotypes in these candidate genes within persons of African descent and European descent. DNA from the CARDIA Year 10 examination (n = 3,950 subjects) will be genotyped for the selected variants that characterize the common haplotypes. Data on the presence of common variants and haplotypes will be incorporated into the CARDIA Study database. Levels of two important intermediate phenotypes, fibrinogen and C-reactive protein (CRP) were previously determined. Non-invasive assessment of coronary atherosclerosis, defined as the presence of coronary artery calcification (CAC), was obtained on CARDIA participants at the Year 15 exam. Analyses will be stratified by race/ethnicity and focus on the associations of the common haplotypes with fibrinogen, CRP, and CAC measured in early adult life. Secondarily, the investigators will explore possible gene-gene and gene-environment interactions. The proposed multi-disciplinary collaboration should enhance the sensitivity and specificity of efforts to assess the associations of common variation in sets of inflammation/thrombosis candidate genes and cardiovascular risk in young adults.

Eligibility criteria: Cardiac cohort participants with DNA

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Washington
name: David Siscovick
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carlson CS, Aldred SF, Lee PK, Tracy RP, Schwartz SM, Rieder M, Liu K, Williams OD, Iribarren C, Lewis EC, Fornage M, Boerwinkle E, Gross M, Jaquish C, Nickerson DA, Myers RM, Siscovick DS, Reiner AP. Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels. Am J Hum Genet. 2005 Jul;77(1):64-77. doi: 10.1086/431366. Epub 2005 May 16.