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C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis

Elevated C-reactive protein (CRP) concentrations in the blood are associated with acute and chronic infections and inflammation. Nevertheless, the functional role of increased CRP in multiple bacterial and viral infections as well as in chronic inflammatory diseases remains unclear. Here, we studied...

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Autores principales: Lepik, Kaido, Annilo, Tarmo, Kukuškina, Viktorija, Kisand, Kai, Kutalik, Zoltán, Peterson, Pärt, Peterson, Hedi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609773/
https://www.ncbi.nlm.nih.gov/pubmed/28922377
http://dx.doi.org/10.1371/journal.pcbi.1005766
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author Lepik, Kaido
Annilo, Tarmo
Kukuškina, Viktorija
Kisand, Kai
Kutalik, Zoltán
Peterson, Pärt
Peterson, Hedi
author_facet Lepik, Kaido
Annilo, Tarmo
Kukuškina, Viktorija
Kisand, Kai
Kutalik, Zoltán
Peterson, Pärt
Peterson, Hedi
author_sort Lepik, Kaido
collection PubMed
description Elevated C-reactive protein (CRP) concentrations in the blood are associated with acute and chronic infections and inflammation. Nevertheless, the functional role of increased CRP in multiple bacterial and viral infections as well as in chronic inflammatory diseases remains unclear. Here, we studied the relationship between CRP and gene expression levels in the blood in 491 individuals from the Estonian Biobank cohort, to elucidate the role of CRP in these inflammatory mechanisms. As a result, we identified a set of 1,614 genes associated with changes in CRP levels with a high proportion of interferon-stimulated genes. Further, we performed likelihood-based causality model selection and Mendelian randomization analysis to discover causal links between CRP and the expression of CRP-associated genes. Strikingly, our computational analysis and cell culture stimulation assays revealed increased CRP levels to drive the expression of complement regulatory protein CD59, suggesting CRP to have a critical role in protecting blood cells from the adverse effects of the immune defence system. Our results show the benefit of integrative analysis approaches in hypothesis-free uncovering of causal relationships between traits.
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spelling pubmed-56097732017-10-17 C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis Lepik, Kaido Annilo, Tarmo Kukuškina, Viktorija Kisand, Kai Kutalik, Zoltán Peterson, Pärt Peterson, Hedi PLoS Comput Biol Research Article Elevated C-reactive protein (CRP) concentrations in the blood are associated with acute and chronic infections and inflammation. Nevertheless, the functional role of increased CRP in multiple bacterial and viral infections as well as in chronic inflammatory diseases remains unclear. Here, we studied the relationship between CRP and gene expression levels in the blood in 491 individuals from the Estonian Biobank cohort, to elucidate the role of CRP in these inflammatory mechanisms. As a result, we identified a set of 1,614 genes associated with changes in CRP levels with a high proportion of interferon-stimulated genes. Further, we performed likelihood-based causality model selection and Mendelian randomization analysis to discover causal links between CRP and the expression of CRP-associated genes. Strikingly, our computational analysis and cell culture stimulation assays revealed increased CRP levels to drive the expression of complement regulatory protein CD59, suggesting CRP to have a critical role in protecting blood cells from the adverse effects of the immune defence system. Our results show the benefit of integrative analysis approaches in hypothesis-free uncovering of causal relationships between traits. Public Library of Science 2017-09-18 /pmc/articles/PMC5609773/ /pubmed/28922377 http://dx.doi.org/10.1371/journal.pcbi.1005766 Text en © 2017 Lepik 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lepik, Kaido
Annilo, Tarmo
Kukuškina, Viktorija
Kisand, Kai
Kutalik, Zoltán
Peterson, Pärt
Peterson, Hedi
C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis
title C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis
title_full C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis
title_fullStr C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis
title_full_unstemmed C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis
title_short C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis
title_sort c-reactive protein upregulates the whole blood expression of cd59 - an integrative analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609773/
https://www.ncbi.nlm.nih.gov/pubmed/28922377
http://dx.doi.org/10.1371/journal.pcbi.1005766
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