9p21 DNA Variants Associated With Coronary Artery Disease Impair Interferon-γ Signalling Response

Study Questions:

How does DNA variation at 9p21 affect vascular disease?


Endothelial and lymphoblastoid cell lines were generated from patients with variation at the 9p21 locus and used to study potential inflammatory signaling mechanisms.


Using a new, open-ended approach to detect long-distance DNA interactions, the authors determined that the enhancer interval containing the high-risk variant physically interacts with other loci that determine the response to inflammatory signals.


The authors concluded that these findings establish a link between coronary artery disease genetic susceptibility and the response to inflammatory signalling in a vascular cell type and, thus, demonstrate the utility of genome-wide association study (GWAS) findings in directing studies to novel genomic loci and biological processes important for disease etiology.


Several GWAS have identified DNA variation at 9p21 with vascular complications. These variants reside in a noncoding region, or gene desert, so the mechanisms by which these variants affect vascular disease have been a mystery. The authors of this study report intriguing, but complex in vitro data associated with 9p21 DNA variation that may shed important biological insight towards this locus with clinical endpoints. While getting closer to a possible mechanistic explanation for the association between 9p21 variation and vascular outcomes, there is still much to be learned before these findings translate into a specific therapeutic intervention.

Clinical Topics: Arrhythmias and Clinical EP, Atherosclerotic Disease (CAD/PAD), Genetic Arrhythmic Conditions

Keywords: Coronary Artery Disease, DNA, Biological Markers, Cardiology, Genome-Wide Association Study, Genetic Predisposition to Disease, Genomics, Interferon-gamma, Biological Processes

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