Abstract 20276: Variants in the CDNK2B Gene on Chromosome 9p21 are Associated with Coronary Artery Disease Events in African American High Risk Families
Background: A 58kb region on chromosome 9p21.3 region has consistently shown strong association with coronary artery disease (CAD) in multiple genome-wide association studies in populations of European and East Asian ancestry. In this study we sought to further characterize the role of genetic variants in 9p21.3 with incident CAD in African American individuals with a strong genetic predisposition for CAD.
Methods and Results: Apparently healthy African American siblings (N=548) of patients with documented CAD <60 years of age were genotyped and followed for incident CAD for up to 17 years. There were 35 total CAD events (sudden death (n=1); MI (n=9); unstable or stable angina with revascularization (n=17); unstable or stable angina with no revascularization (n=8)) in African Americans at an average follow-up of 8.1 ±3 years range 5 to 17 years). Tests for association of 99 SNPs across the 9p21.3 region in a GEE logistic framework under an additive model, adjusting for multiple traditional risk factors follow-up time, and population stratification were performed. A single SNP in African Americans within the CDKN2B gene met stringent criteria for statistical significance, including permutation-based evaluations. The association signal at a common variant, rs3217989, (OR=0.19, 95% CI: 0.07 to 0.50, p=0.0008) conveying protection against CAD was replicated in two additional cohorts of prevalent CAD/MI in African Americans (N=990, p=0.024, OR= 0.779, 95% CI: 0.626-0.968).
Conclusions:: This is the first report of association signal in a population of African ancestry with a common variant within the CDKN2B gene ∼115kb away and independent from previous published findings in European and East Asian ancestry populations. We demonstrate significant association with occurrence of CAD events in high-risk African American siblings of persons with premature CAD, findings supported by replication data on two additional African American cohorts.
- © 2010 by American Heart Association, Inc.