title: Single nucleotide variants in the protein C pathway and mortality in dialysis patients.
abstract: BACKGROUND
  The protein C pathway plays an important role in the maintenance of endothelial barrier function and in the inflammatory and coagulant processes that are characteristic of patients on dialysis. We investigated whether common single nucleotide variants (SNV) in genes encoding protein C pathway components were associated with all-cause 5 years mortality risk in dialysis patients.
  
  
  METHODS
  Single nucleotides variants in the factor V gene (F5 rs6025; factor V Leiden), the thrombomodulin gene (THBD rs1042580), the protein C gene (PROC rs1799808 and 1799809) and the endothelial protein C receptor gene (PROCR rs867186, rs2069951, and rs2069952) were genotyped in 1070 dialysis patients from the NEtherlands COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort) and in 1243 dialysis patients from the German 4D cohort.
  
  
  RESULTS
  Factor V Leiden was associated with a 1.5-fold (95% CI 1.1-1.9) increased 5-year all-cause mortality risk and carriers of the AG/GG genotypes of the PROC rs1799809 had a 1.2-fold (95% CI 1.0-1.4) increased 5-year all-cause mortality risk. The other SNVs in THBD, PROC, and PROCR were not associated with 5-years mortality.
  
  
  CONCLUSIONS
  Our study suggests that factor V Leiden and PROC rs1799809 contributes to an increased mortality risk in dialysis patients.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Gürbey
authors.initials: G
authors.lastname: Ocak
authors.affiliation: Department of Medicine, Division of Nephrology, University Hospital, Würzburg, Germany; Comprehensive Heart Failure Center, University of Wuerzburg, Wuerzburg, Germany; Institute of Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Carla Y
authors.initials: CY
authors.lastname: Vossen
authors.affiliation: Department of Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Vos
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.affiliation: Department of Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Pieter H
authors.initials: PH
authors.lastname: Reitsma
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.affiliation: Department of Public Health, Social and Preventive Medicine, University of Heidelberg, Mannheim, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Department of Hematology, University of Cambridge and National Health Service Blood and Transplant, Cambridge, United Kingdom; Department of Human Genetics, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.affiliation: Department of Nephrology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Krediet
authors.affiliation: Hans Mak Institute, Naarden, The Netherlands.
authors.forename: Elisabeth W
authors.initials: EW
authors.lastname: Boeschoten
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Friedo W
authors.initials: FW
authors.lastname: Dekker
authors.affiliation: Department of Medicine, Division of Nephrology, University Hospital, Würzburg, Germany; Comprehensive Heart Failure Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marion
authors.initials: M
authors.lastname: Verduijn
mesh_terms: D015703:Antigens, CD / Q000235:genetics; D000074283:Endothelial Protein C Receptor; D005165:Factor V / Q000235:genetics*; D005858:Germany; D006801:Humans; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011486:Protein C / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D006435:Renal Dialysis / Q000401:mortality*; D015398:Signal Transduction / Q000235:genetics*; D018180:Thrombomodulin / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011486:Protein C; D011956:Receptors, Cell Surface; D018180:Thrombomodulin; C095381:factor V Leiden; D005165:Factor V