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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.

Publication ,  Journal Article
Dennis, J; Johnson, CY; Adediran, AS; de Andrade, M; Heit, JA; Morange, P-E; Trégouët, D-A; Gagnon, F
Published in: Blood
March 8, 2012

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 The present study is a highly comprehensive systematic review and meta-analysis, including unpublished genome-wide association study results, conducted to evaluate the evidence for an association between rs867186 and 2 common thrombotic outcomes, venous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.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

March 8, 2012

Volume

119

Issue

10

Start / End Page

2392 / 2400

Location

United States

Related Subject Headings

  • Venous Thromboembolism
  • Thrombosis
  • Risk Assessment
  • Receptors, Cell Surface
  • Polymorphism, Single Nucleotide
  • Myocardial Infarction
  • Immunology
  • Humans
  • Genome-Wide Association Study
  • Endothelial Protein C Receptor
 

Citation

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Dennis, J., Johnson, C. Y., Adediran, A. S., de Andrade, M., Heit, J. A., Morange, P.-E., … Gagnon, F. (2012). 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. Blood, 119(10), 2392–2400. https://doi.org/10.1182/blood-2011-10-383448
Dennis, Jessica, Candice Y. Johnson, Adeniyi Samuel Adediran, Mariza de Andrade, John A. Heit, Pierre-Emmanuel Morange, David-Alexandre Trégouët, and France Gagnon. “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.Blood 119, no. 10 (March 8, 2012): 2392–2400. https://doi.org/10.1182/blood-2011-10-383448.
Dennis J, Johnson CY, Adediran AS, de Andrade M, Heit JA, Morange P-E, et al. 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. Blood. 2012 Mar 8;119(10):2392–400.
Dennis, Jessica, et al. “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.Blood, vol. 119, no. 10, Mar. 2012, pp. 2392–400. Pubmed, doi:10.1182/blood-2011-10-383448.
Dennis J, Johnson CY, Adediran AS, de Andrade M, Heit JA, Morange P-E, Trégouët D-A, Gagnon F. 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. Blood. 2012 Mar 8;119(10):2392–2400.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

March 8, 2012

Volume

119

Issue

10

Start / End Page

2392 / 2400

Location

United States

Related Subject Headings

  • Venous Thromboembolism
  • Thrombosis
  • Risk Assessment
  • Receptors, Cell Surface
  • Polymorphism, Single Nucleotide
  • Myocardial Infarction
  • Immunology
  • Humans
  • Genome-Wide Association Study
  • Endothelial Protein C Receptor