Paper of the Month

May 2017

Functional Characterization of the GUCY1A3 Coronary Artery Disease Risk Locus, Circulation, doi: 10.1161/CIRCULATIONAHA.116.024152, DZHK authors: Kessler, Wobst, Wolf, Vilne, Dang, Sager, Kastrati, Erdmann, Kaiser, Schunkert

DZHK researchers from the Munich and Lübeck sites have succeeded in decoding an important mechanism of action in the inheritance of coronary artery disease (CAD). In previous studies (among others, Erdmann et al., Nature, 2013), the researchers were already able to demonstrate the importance of the GUCY1A3 gene in the inheritance of CAD. It was established that rare mutations as well as a common variant play a role. Now the researchers have shown that the common risk allele of this CAD gene leads to decreased formation of a sub-unit of the soluble guanylate cyclase by destroying a transcription factor binding site. In affected individuals, who account for about 50 percent of the population, this in turn causes reduced inhibition of platelet aggregation and altered migration from vascular smooth muscle cells. These represent significant changes in key processes of atherosclerotic plaque formation and rupture. The findings of this study may help to develop new strategies to prevent and treat CAD and to apply them on an individualized basis according to genetic predisposition.