Advances in biology suggest that atherosclerosis may reflect, in part, the vascular consequences of chronic inflammation. Using information on complete sequence variation and common haplotypes on a set of candidate genes generated through the NHLBI Program in Genomic Applications (PGA) at the University of Washington, we propose 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 Adult (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 PGA, we 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, we 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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL071017-04
Application #
6929772
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Jaquish, Cashell E
Project Start
2002-08-16
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
4
Fiscal Year
2005
Total Cost
$557,412
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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