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Muehlschlegel, J.D.* ; Perry, T.E.* ; Liu, K.Y.* ; Fox, A.A.* ; Smith, S.A.* ; Lichtner, P. ; Collard, C.D.* ; Shernan, S.K.* ; Hartwig, J.H.* ; Body, S.C.* ; Hoffmeister, K.M.*

Polymorphism in the protease-activated receptor-4 gene region associates with platelet activation and perioperative myocardial injury.

Am. J. Hematol. 87, 161-166 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Protease-activated receptors (PAR)-1 and -4 are the principal receptors for thrombin-mediated platelet activation. Functional genetic variation has been described in the human PAR1 gene, but not in the PAR4 gene (F2RL3). We sought to identify variants in and around F2RL3 and to determine their association with perioperative myocardial injury (PMI) after coronary artery bypass graft surgery. We further explored possible mechanisms for F2RL3 single nucleotide polymorphism (SNP) associations with PMI including altered receptor expression and platelet activation. Twenty-three SNPs in the F2RL3 gene region were genotyped in two phases in 934 Caucasian subjects. Platelets from 43 subjects (23 major allele, 20 risk allele) homozygous for rs773857 (SNP with the strongest association with PMI) underwent flow cytometry to assess PAR4 receptor number and response to activation by a specific PAR4 activating peptide (AYPGKF) measured by von Willebrand factor (vWf) binding and P-selectin release and PAC-1 binding. We identified a novel association of SNP rs773857 with PMI (OR = 2.4, P = 0.004). rs773857 risk allele homozygotes have significantly increased platelet counts and platelets showed a significant increase in P-selectin release after activation (P = 0.004). We conclude that rs773857 risk allele homozygotes are associated with risk for increased platelet count and hyperactivity.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords CARDIAC TROPONIN-I; CORONARY-ARTERY-DISEASE; HUMAN GENOME; ISCHEMIA/REPERFUSION INJURY; CARDIOVASCULAR-DISEASE; TRANSCRIPTION FACTOR; INFARCTION; SURGERY; RISK; THROMBOSIS
ISSN (print) / ISBN 0361-8609
e-ISSN 1096-8652
Journal American Journal of Hematology
Quellenangaben Volume: 87, Issue: 2, Pages: 161-166 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)