Cardiovascular Diseases Clinical Trial
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.
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.
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