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Single Nucleotide Variants in the Protein C Pathway and Mortality in Dialysis Patients

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 pa...

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Autores principales: Ocak, Gürbey, Drechsler, Christiane, Vossen, Carla Y., Vos, Hans L., Rosendaal, Frits R., Reitsma, Pieter H., Hoffmann, Michael M., März, Winfried, Ouwehand, Willem H., Krediet, Raymond T., Boeschoten, Elisabeth W., Dekker, Friedo W., Wanner, Christoph, Verduijn, Marion
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016291/
https://www.ncbi.nlm.nih.gov/pubmed/24816905
http://dx.doi.org/10.1371/journal.pone.0097251
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author Ocak, Gürbey
Drechsler, Christiane
Vossen, Carla Y.
Vos, Hans L.
Rosendaal, Frits R.
Reitsma, Pieter H.
Hoffmann, Michael M.
März, Winfried
Ouwehand, Willem H.
Krediet, Raymond T.
Boeschoten, Elisabeth W.
Dekker, Friedo W.
Wanner, Christoph
Verduijn, Marion
author_facet Ocak, Gürbey
Drechsler, Christiane
Vossen, Carla Y.
Vos, Hans L.
Rosendaal, Frits R.
Reitsma, Pieter H.
Hoffmann, Michael M.
März, Winfried
Ouwehand, Willem H.
Krediet, Raymond T.
Boeschoten, Elisabeth W.
Dekker, Friedo W.
Wanner, Christoph
Verduijn, Marion
author_sort Ocak, Gürbey
collection PubMed
description 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. CONCLUSION: Our study suggests that factor V Leiden and PROC rs1799809 contributes to an increased mortality risk in dialysis patients.
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spelling pubmed-40162912014-05-14 Single Nucleotide Variants in the Protein C Pathway and Mortality in Dialysis Patients Ocak, Gürbey Drechsler, Christiane Vossen, Carla Y. Vos, Hans L. Rosendaal, Frits R. Reitsma, Pieter H. Hoffmann, Michael M. März, Winfried Ouwehand, Willem H. Krediet, Raymond T. Boeschoten, Elisabeth W. Dekker, Friedo W. Wanner, Christoph Verduijn, Marion PLoS One Research Article 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. CONCLUSION: Our study suggests that factor V Leiden and PROC rs1799809 contributes to an increased mortality risk in dialysis patients. Public Library of Science 2014-05-09 /pmc/articles/PMC4016291/ /pubmed/24816905 http://dx.doi.org/10.1371/journal.pone.0097251 Text en © 2014 Ocak et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ocak, Gürbey
Drechsler, Christiane
Vossen, Carla Y.
Vos, Hans L.
Rosendaal, Frits R.
Reitsma, Pieter H.
Hoffmann, Michael M.
März, Winfried
Ouwehand, Willem H.
Krediet, Raymond T.
Boeschoten, Elisabeth W.
Dekker, Friedo W.
Wanner, Christoph
Verduijn, Marion
Single Nucleotide Variants in the Protein C Pathway and Mortality in Dialysis Patients
title Single Nucleotide Variants in the Protein C Pathway and Mortality in Dialysis Patients
title_full Single Nucleotide Variants in the Protein C Pathway and Mortality in Dialysis Patients
title_fullStr Single Nucleotide Variants in the Protein C Pathway and Mortality in Dialysis Patients
title_full_unstemmed Single Nucleotide Variants in the Protein C Pathway and Mortality in Dialysis Patients
title_short Single Nucleotide Variants in the Protein C Pathway and Mortality in Dialysis Patients
title_sort single nucleotide variants in the protein c pathway and mortality in dialysis patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016291/
https://www.ncbi.nlm.nih.gov/pubmed/24816905
http://dx.doi.org/10.1371/journal.pone.0097251
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