Commentary
PROCR vascular disease locus: elucidating mechanisms of genetic cross-disease correlations is a priority
Author(s): Nicole Watson*
Numerous genetic risk loci have been linked to a variety of prevalent human diseases. However, the molecular basis of pleiotropy is frequently unknown. The PROCR locus is linked to a lower risk of coronary artery disease (CAD) but a higher risk of venous thromboembolism (VTE). We provide an integrative method to uncover the molecular mechanism behind the PROCR locus. PROCR-p. Ser219Gly is identified as the likely causing mutation at the locus, while protein C is identified as a causal component. We show that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, reducing leukocyte–endothelial cell adhesion and vascular inflammation, using genetic analyses, human recall-by-genotype, and in vitro experimentation. PROCR-219Gly is also linked to an enhanced pro-thrombotic state via coagula.. Read More»
DOI:
10.37532/pulcj.22.6(2).19-20
+447362049920
