title: The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies.
abstract: The endothelial protein C receptor (EPCR) limits thrombus formation by enhancing activation of the protein C anticoagulant pathway, and therefore may play a role in the etiology of thrombotic disorders. The rs867186 single-nucleotide polymorphism in the PROCR gene (g.6936A > G, c.4600A > G), resulting in a serine-to-glycine substitution at codon 219, has been associated with reduced activation of the protein C pathway, although its association with thrombosis risk remains unclear. The present study is a highly comprehensive systematic review and meta-analysis, including unpublished genome-wide association study results, conducted to evaluate the evidence for an association between rs867186 and 2 common thrombotic outcomes, venous thromboembolism (VTE) and myocardial infarction (MI), which are hypothesized to share some etiologic pathways. MEDLINE, EMBASE, and HuGE Navigator were searched through July 2011 to identify relevant epidemiologic studies, and data were summarized using random-effects meta-analysis. Twelve candidate genes and 13 genome-wide association studies were analyzed (11 VTE and 14 MI, including 37,415 cases and 84,406 noncases). Under the additive genetic model, the odds of VTE increased by a factor of 1.22 (95% confidence interval, 1.11-1.33, P < .001) for every additional copy of the G allele. No evidence for association with MI was observed.
authors.affiliation: Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, ON, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Dennis
authors.forename: Candice Y
authors.initials: CY
authors.lastname: Johnson
authors.forename: Adeniyi Samuel
authors.initials: AS
authors.lastname: Adediran
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: John A
authors.initials: JA
authors.lastname: Heit
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Trégouët
authors.forename: France
authors.initials: F
authors.lastname: Gagnon
mesh_terms: D019943:Amino Acid Substitution; D015703:Antigens, CD; D016208:Databases, Factual; D000074283:Endothelial Protein C Receptor; D055106:Genome-Wide Association Study; D006801:Humans; D009203:Myocardial Infarction / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface; D018570:Risk Assessment; D013927:Thrombosis / Q000235:genetics*; D054556:Venous Thromboembolism / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011956:Receptors, Cell Surface