Functional Characterization of the <i>GUCY1A3</i> Coronary Artery Disease Risk Locus

Abstract

Rs7692387 is located in an intronic site that modulates <i>GUCY1A3</i> promoter activity. The transcription factor ZEB1 binds preferentially to the nonrisk allele, leading to an increase in <i>GUCY1A3</i> expression, higher sGC levels, and higher sGC activity after stimulation. Finally, human and mouse data link augmented sGC expression to lower risk of atherosclerosis.