title: A 23bp insertion in the endothelial protein C receptor (EPCR) gene impairs EPCR function.
abstract: EPCR is a type I transmembrane protein, highly expressed on the endothelium of large vessels, that binds protein C and augments its activation. In this study, a 23bp insertion in the EPCR gene was found in 4/198 survivors of myocardial infarction and 3/194 patients with deep vein thrombosis. The EPCR gene with the insertion predicts a protein that lacks part of the extracellular domain, the transmembrane domain and the cytoplasmic tail. Expression studies showed that the truncated protein is not localized on the cell surface, cannot be secreted in the culture medium, and does not bind activated protein C. Since protein C activation depends on the concentration of EPCR, patients with the EPCR insertion could have a diminished protein C activation capacity. Further clinical studies of adequate samples size are necessary to establish whether or not the EPCR insertion predisposes to the development of thrombotic events.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy. eugeniabiguzzi@yahoo.it
authors.forename: E
authors.initials: E
authors.lastname: Biguzzi
authors.forename: G
authors.initials: G
authors.lastname: Merati
authors.forename: P C
authors.initials: PC
authors.lastname: Liaw
authors.forename: P
authors.initials: P
authors.lastname: Bucciarelli
authors.forename: N
authors.initials: N
authors.lastname: Oganesyan
authors.forename: D
authors.initials: D
authors.lastname: Qu
authors.forename: J M
authors.initials: JM
authors.lastname: Gu
authors.forename: R
authors.initials: R
authors.lastname: Fetiveau
authors.forename: C T
authors.initials: CT
authors.lastname: Esmon
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
authors.forename: E M
authors.initials: EM
authors.lastname: Faioni
mesh_terms: D000328:Adult; D017668:Age of Onset; D000818:Animals; D001779:Blood Coagulation Factors; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004730:Endothelium, Vascular / Q000378:metabolism*; D004789:Enzyme Activation; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006031:Glycosylation; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D016254:Mutagenesis, Insertional; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D010865:Pilot Projects; D011485:Protein Binding / Q000235:genetics; D011486:Protein C / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D013329:Structure-Activity Relationship; D019851:Thrombophilia / Q000453:epidemiology / Q000235:genetics*; D020246:Venous Thrombosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D001779:Blood Coagulation Factors; D011486:Protein C; D011956:Receptors, Cell Surface; C091963:activated protein C receptor