Targeted gene sequencing identifies variants in the protein c and endothelial protein c receptor genes in patients with unprovoked venous thromboembolism

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 33, Issue 11, 2013, Pages 2674-2681

  Wu, Cynthia ^a   Dwivedi, Dhruva J ^b,c   Pepler, Laura ^b,c   Lysov, Zakhar ^b,c   Waye, John ^b   Julian, Jim ^b   Desch, Karl ^d   Ginsburg, David ^d   Weitz, Jeffrey I ^b   Kearon, Clive ^b   Liaw, Patricia C ^b,c  

^a UNIVERSITY OF ALBERTA   (Canada)

^b MCMASTER UNIVERSITY   (Canada)

^c MCMASTER UNIVERSITY   (Canada)

^d UNIVERSITY OF MICHIGAN   (United States)

Author keywords

endothelial cell protein C receptor; genes; polymorphism, genetic; protein C; venous thromboembolism

Indexed keywords

ENDOTHELIAL PROTEIN C RECEPTOR; FLUORESCENT DYE; PROTEIN C; WARFARIN;

ADULT; AMINO ACID SUBSTITUTION; ARTICLE; CELL STRAIN HEK293; CONTROLLED STUDY; DNA SEQUENCE; EXON; FEMALE; GENE OVEREXPRESSION; GENETIC RISK; GENETIC VARIABILITY; HAPLOTYPE; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; MALE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS; RISK ASSESSMENT; SINGLE NUCLEOTIDE POLYMORPHISM; VENOUS THROMBOEMBOLISM; WESTERN BLOTTING;

ENDOTHELIAL CELL PROTEIN C RECEPTOR; GENES; POLYMORPHISM, GENETIC; PROTEIN C; VENOUS THROMBOEMBOLISM;

ADULT; AGED; ANTIGENS, CD; ENDOTHELIUM, VASCULAR; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; HAPLOTYPES; HEK293 CELLS; HUMANS; MALE; MIDDLE AGED; PROTEIN C; RECEPTORS, CELL SURFACE; RISK FACTORS; VENOUS THROMBOEMBOLISM;

EID: 84887072143     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.113.302137     Document Type: Article

References (38)

1. Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT. The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci USA. 1996;93:10212-10216.
2. Taylor FB Jr, Peer GT, Lockhart MS, Ferrell G, Esmon CT. Endothelial cell protein C receptor plays an important role in protein C activation in vivo. Blood. 2001;97:1685-1688.
3. Kearon C, Julian JA, Kovacs MJ, et al; ELATE Investigators. Infuence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial. Blood. 2008;112:4432-4436.
4. Simioni P, Tormene D, Spiezia L, Tognin G, Rossetto V, Radu C, Prandoni P. Inherited thrombophilia and venous thromboembolism. Semin Thromb Hemost. 2006;32:700-708.
5. De Stefano V, Rossi E, Za T, Leone G. Prophylaxis and treatment of venous thromboembolism in individuals with inherited thrombophilia. Semin Thromb Hemost. 2006;32:767-780.
6. Walker PA, Bauer KA, McDonagh J. A simple, automated functional assay for protein C. Am J Clin Pathol. 1989;92:210-213.
7. Martinoli JL, Stocker K. Fast functional protein C assay using Protac, a novel protein C activator. Thromb Res. 1986;43:253-264.
8. Gempeler-Messina PM, Volz K, Bühler B, Müller C. Protein C activators from snake venoms and their diagnostic use. Haemostasis. 2001;31: 266-272.
9. Esmon CT. The endothelial cell protein C receptor. Thromb Haemost. 2000;83:639-643.
10. Esmon CT. Protein-C: biochemistry, physiology, and clinical implications. Blood. 1983;62:1155-1158.
11. Esmon CT. The protein C pathway. Chest. 2003;124(3 Suppl):26S-32S.
12. Oganesyan V, Oganesyan N, Terzyan S, Qu D, Dauter Z, Esmon NL, Esmon CT. The crystal structure of the endothelial protein C receptor and a bound phospholipid. J Biol Chem. 2002;277:24851-24854.
13. Liaw PC, Mather T, Oganesyan N, Ferrell GL, Esmon CT. Identifcation of the protein C/activated protein C binding sites on the endothelial cell protein C receptor. Implications for a novel mode of ligand recognition by a major histocompatibility complex class 1-type receptor. J Biol Chem. 2001;276:8364-8370.
14. Kearon C, Ginsberg JS, Kovacs MJ, et al; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med. 2003;349:631-639.
15. Saposnik B, Reny JL, Gaussem P, Emmerich J, Aiach M, Gandrille S. A hap-lotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis. Blood. 2004;103:1311-1318.
16. Qu D, Wang Y, Song Y, Esmon NL, Esmon CT. The Ser219->Gly dimorphism of the endothelial protein C receptor contributes to the higher soluble protein levels observed in individuals with the A3 haplotype. J Thromb Haemost. 2006;4:229-235.
17. den Dunnen JT, Antonarakis SE. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat. 2000;15:7-12.
18. Miletich JP, Broze GJ Jr. Beta protein C is not glycosylated at aspara-gine 329. The rate of translation may infuence the frequency of usage at asparagine-X-cysteine sites. J Biol Chem. 1990;265:11397-11404.
19. Fukudome K, Esmon CT. Identifcation, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem. 1994;269:26486-26491.
20. Biguzzi E, Merati G, Liaw PC, Bucciarelli P, Oganesyan N, Qu D, Gu JM, Fetiveau R, Esmon CT, Mannucci PM, Faioni EM. A 23bp insertion in the endothelial protein C receptor (EPCR) gene impairs EPCR function. Thromb Haemost. 2001;86:945-948.
21. Grinnell BW, Walls JD, Gerlitz B. Glycosylation of human protein C affects its secretion, processing, functional activities, and activation by thrombin. J Biol Chem. 1991;266:9778-9785.
22. Simioni P, Kalafatis M, Millar DS, Henderson SC, Luni S, Cooper DN, Girolami A. Compound heterozygous protein C defciency resulting in the presence of only the beta-form of protein C in plasma. Blood. 1996;88:2101-2108.
23. Wojcik EG, Simioni P, d Berg M, Girolami A, Bertina RM. Mutations which introduce free cysteine residues in the Gla-domain of vitamin K dependent proteins result in the formation of complexes with alpha 1-microglobulin. Thromb Haemost. 1996;75:70-75.
24. Preston RJ, Villegas-Mendez A, Sun YH, Hermida J, Simioni P, Philippou H, Dahlbäck B, Lane DA. Selective modulation of protein C affnity for EPCR and phospholipids by Gla domain mutation. FEBS J. 2005;272:97-108.
25. Fukudome K, Ye X, Tsuneyoshi N, Tokunaga O, Sugawara K, Mizokami H, Kimoto M. Activation mechanism of anticoagulant protein C in large blood vessels involving the endothelial cell protein C receptor. J Exp Med. 1998;187:1029-1035.
26. Gu JM, Crawley JT, Ferrell G, Zhang F, Li W, Esmon NL, Esmon CT. Disruption of the endothelial cell protein C receptor gene in mice causes placental thrombosis and early embryonic lethality. J Biol Chem. 2002;277:43335-43343.
27. von Depka M, Czwalinna A, Eisert R, Wermes C, Scharrer I, Ganser A, Ehrenforth S. Prevalence of a 23bp insertion in exon 3 of the endothelial cell protein C receptor gene in venous thrombophilia. Thromb Haemost. 2001;86:1360-1362.
28. Akar N, Gökdemir R, Ozel D, Akar E. Endothelial cell protein C receptor (EPCR) gene exon III, 23 bp insertion mutation in the Turkish pediatric thrombotic patients. Thromb Haemost. 2002;88:1068-1069.
29. Poort SR, Vos HL, Rosendaal FR, Bertina RM. The endothelial protein C receptor (EPCR) 23 bp insert mutation and the risk of venous thrombosis. Thromb Haemost. 2002;88:160-162.
30. Galligan L, Livingstone W, Mynett-Johnston L, Smith OP. Prevalence of the 23bp endothelial protein C receptor (EPCR) gene insertion in the Irish population. Thromb Haemost. 2002;87:773-774.
31. Stearns-Kurosawa DJ, Burgin C, Parker D, Comp P, Kurosawa S. Bimodal distribution of soluble endothelial protein C receptor levels in healthy populations. J Thromb Haemost. 2003;1:855-856.
32. Stearns-Kurosawa DJ, Swindle K, D'Angelo A, Della Valle P, Fattorini A, Caron N, Grimaux M, Woodhams B, Kurosawa S. Plasma levels of endothelial protein C receptor respond to anticoagulant treatment. Blood. 2002;99:526-530.
33. Qu D, Wang Y, Esmon NL, Esmon CT. Regulated endothelial protein C receptor shedding is mediated by tumor necrosis factor-alpha converting enzyme/ADAM17. J Thromb Haemost. 2007;5:395-402.
34. Trégouët DA, Heath S, Saut N, Biron-Andreani C, Schved JF, Pernod G, Galan P, Drouet L, Zelenika D, Juhan-Vague I, Alessi MC, Tiret L, Lathrop M, Emmerich J, Morange PE. Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach. Blood. 2009;113:5298-5303.
35. Heit JA, Armasu SM, Asmann YW, Cunningham JM, Matsumoto ME, Petterson TM, De Andrade M. A genome-wide association study of venous thromboembolism identifes risk variants in chromosomes 1q24.2 and 9q. J Thromb Haemost. 2012;10:1521-1531.
36. Tang W, Teichert M, Chasman DI, et al. A genome-wide association study for venous thromboembolism: the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium. Genet Epidemiol. 2013;37:512-521.
37. Gorlov IP, Gorlova OY, Sunyaev SR, Spitz MR, Amos CI. Shifting paradigm of association studies: value of rare single-nucleotide polymorphisms. Am J Hum Genet. 2008;82:100-112.
38. Schork NJ, Murray SS, Frazer KA, Topol EJ. Common vs. rare allele hypotheses for complex diseases. Curr Opin Genet Dev. 2009;19:212-219.