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

TitreC-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis.
Publication TypeJournal Article
Year of Publication2017
AuthorsLepik, K, Annilo, T, Kukuškina, V, Kisand, K, Kutalik, Z, Peterson, P, Peterson, H
Corporate AuthorseQTLGen Consortium
JournalPLoS computational biology
Volume13
Issue9
Paginatione1005766
Date Published09/2017
DOI10.1371/journal.pcbi.1005766
ISSN1553-7358
Mots-clésAdult, Antigens, CD59, C-Reactive Protein, Cohort Studies, Estonia, Humans, Inflammation, Up-Regulation
Abstract

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.

Alternate URL

http://www.ncbi.nlm.nih.gov/pubmed/28922377?dopt=Abstract

WOS ID (UT)

000411981000043

Alternate JournalPLoS Comput. Biol.
Citation Key / SERVAL ID8267
Peer reviewRefereed
PubMed ID28922377
PubMed Central IDPMC5609773

                         

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