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Cited by 16Blood Coagulation and Thrombosis MechanismsComplement system in diseasesGenetic Associations and Epidemiology

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High levels of protein C are determined by PROCR haplotype 3

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PINTAO, M.C., ROSHANI, S., DE VISSER, M.C.H., TIEKEN, C., TANCK, M.W.T., WICHERS, I.M., MEIJERS, J.C.M., ROSENDAAL, F.R., MIDDELDORP, S., REITSMA, P.H.·2011·Journal of Thrombosis and Haemostasis
DOI 10.1111/j.1538-7836.2011.04256.x
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Abstract

Background Genetic determinants of plasma levels of protein C (PC) are poorly understood. Recently, we identified a locus on chromosome 20 determining high PC levels in a large Dutch pedigree with unexplained thrombophilia. Candidate genes in the LOD-1 support interval included FOXA2, THBD and PROCR. Objectives To examine these candidate genes and their influence on plasma levels of PC. Patients/methods Exons, promoter and 3'UTR of the candidate genes were sequenced in 12 family members with normal to high PC levels. Four haplotypes of PROCR, two SNPs in the neighboring gene EDEM2 and critical SNPs encountered during resequencing were genotyped in the family and in a large group of healthy individuals (the Leiden Thrombophilia Study (LETS) controls). Soluble endothelial protein C receptor (sEPCR) and soluble thrombomodulin (sTM) plasma levels were measured in the family. Results PROCR haplotype 3 (H3) and FOXA2 rs1055080 were associated with PC levels in the family but only PROCR H3 was also associated with plasma levels in the healthy individuals. Carriers of both variants had higher PC levels than carriers of only PROCR H3 in the family but not in healthy individuals, suggesting that a second determinant is present. EDEM2 SNPs were associated with PC levels, but their effect was small. PC and sEPCR levels were associated in both studies. sTM was not associated with variations of THBD or PC levels. Conclusions Chromosome 20 harbors genetic determinants of PC and sEPCR levels and the analysis of candidate genes suggests that the PROCR locus is responsible.

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Crossref · 10.1111/j.1538-7836.2011.04256.x

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  • The coding PROCR variant p.Ser219Gly (rs867186) has been associated with higher levels of protein C and soluble EPCR.

    “which has been associated with both venous thromboembolism 54,55 and higher levels of protein C and soluble EPCR.56,57”

    From Meta-analysis of ACE inhibitor-induced angioedema identifies novel risk locus. (2024) · cites this paper as [57]

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Metadata

Authors
PINTAO, M. C., ROSHANI, S., DE VISSER, M. C. H., TIEKEN, C., TANCK, M. W. T., WICHERS, I. M., MEIJERS, J. C. M., ROSENDAAL, F. R., MIDDELDORP, S., & REITSMA, P. H.
Affiliations
  • Leiden University Medical Center (NL)
  • Amsterdam UMC Location University of Amsterdam (NL)
Corresponding author
REITSMA, P.H.
ORCID
Venue
Journal of Thrombosis and Haemostasis
Publisher
Elsevier BV
Published
2011-05
Volume
9
Issue
5
Pages
969-976
ISSN
1538-7836 (ISSN-L)
DOI
10.1111/j.1538-7836.2011.04256.x
OpenAlex
W2123622015
Cited by
16
References
1
Citations by year
2024: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2018: 1 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 2
FWCI
1.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Thrombosis and Haemostasis (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
protein C, protein C receptor, FOXA2, thrombomodulin, soluble endothelial protein C receptor, soluble thrombomodulin, thrombophilia, chromosome 20
MeSH terms
Endothelial Protein C Receptor, Adult, Child, Preschool, Chromosomes, Human, Pair 20, Exons, Female, Haplotypes, Humans, Genetic Linkage, Male, Pedigree, Promoter Regions, Genetic, Protein C, Receptors, Cell Surface, Genetic Variation, Antigens, CD, Thrombomodulin, 3' Untranslated Regions

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