Abstract 15730: Serum Interferon Alpha 21 is a Biomarker of the 9p21.3 Risk Locus for Coronary Artery Disease
Background - The 9p21.3 locus confers risk for coronary artery disease (CAD) by an unknown mechanism. A recent report identified several long-range enhancers, at CDKN2B, CDKN2A, MTAP and between the interferon ω-1 (IFNW1) and interferon α-21 (IFNA21) genes, whose chromatin structure is influenced by single nucleotide polymorphisms within the 9p21.3 risk locus as far as 1 million base pairs away. Here, we tested whether protein expression from the genes in the vicinity of these long-range enhancers correlates with the 9p21.3 risk genotype.
Methods and Results - Using immunoblot analysis of protein extracts from primary cultures of human aortic smooth muscle cells (n=6) and peripheral blood lymphocytes from patients with CAD (n=18) genotyped for the 9p21.3 risk locus using SNP microarrays, we found that CDKN2A protein expression in both cell types, and CDKN2B protein expression in aortic smooth muscle cells was negatively associated with 9p21.3 risk genotype. No association between MTAP expression and 9p21.3 genotype was seen in either cell type. However, a strong positive correlation (p<10-4) between IFNA21 levels and 9p21.3 risk genotype was seen in both cell types. Importantly, ELISA analysis of serum from 242 genotyped CAD patients showed highly elevated levels of IFNA21 in individuals homozygous for the 9p21.3 risk allele (p=1.38x10-50).
Conclusion - Elevated serum IFNA21 is a biomarker for the 9p21.3 CAD risk locus. Together with reduced CDKN2A protein expression, elevated IFNA21 may account for the risk of CAD associated with the 9p21.3 locus.
- © 2011 by American Heart Association, Inc.