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J Am Coll Cardiol. 2013 Jan 15;61(2):143-7. doi: 10.1016/j.jacc.2012.08.1020. Epub 2012 Nov 28.

Interferon-γ activates expression of p15 and p16 regardless of 9p21.3 coronary artery disease risk genotype.

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  • 1Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.



Because post-transcriptional mechanisms modulate levels of p16 (encoded by CDKN2A) and p15 (encoded by CDKN2B), we tested whether interferon-γ regulates the expression of these proteins and the effect of the 9p21 genotype.


The mechanism whereby the common variant at chromosome 9p21.3 confers risk for coronary artery disease (CAD) remains uncertain. A recent report proposed that 9p21.3 confers differential activation of adjacent genes in response to interferon-γ, and reported that mRNA levels of CDKN2B are reduced in response to interferon-γ.


Human umbilical vein endothelial cells (HUVECs), aortic smooth muscle cells, HeLa cells, HEK293 cells, and 16 human lymphoblastoid cell lines, all genotyped for the 9p21.3 locus, were treated with interferon-γ and analyzed by immunoblot.


In all cells tested--except HUVECs where expression was not modulated by interferon-γ--regardless of 9p21.3 genotype, interferon-γ increased the expression of p16 and p15. Northern blot analysis confirmed that interferon-γ has little effect on mRNA levels of CDKN2A and CDKN2B.


The 9p21.3 risk genotype does not affect the activation of cyclin-dependent kinase inhibitors p15 and p16 by interferon-γ. Thus, another mechanism is likely to account for the CAD risk associated with this locus.

Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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