A Genome Wide Association Study on plasma FV levels identified PLXDC2 as a new modifier of the coagulation process

Background Factor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation process. Objective To detect novel genetic loci participating to the regulation of FV plasma levels. Methods We conducted the first Genome Wi...

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Published inJournal of thrombosis and haemostasis Vol. 17; no. 11; pp. 1808 - 1814
Main Authors Thibord, Florian, Hardy, Lise, Ibrahim‐Kosta, Manal, Saut, Noémie, Pulcrano‐Nicolas, Anne‐Sophie, Goumidi, Louisa, Civelek, Mete, Eriksson, Per, Deleuze, Jean‐François, Le Goff, Wilfried, Trégouët, David‐Alexandre, Morange, Pierre‐Emmanuel
Format Journal Article
LanguageEnglish
Published England Elsevier Limited 01.11.2019
Wiley
Subjects
biomarkers
Coagulation
coagulation factor
Coagulation factors
computational biology
Factor V
Gene expression
Gene loci
Genetic diversity
genetics
Genome-wide association studies
Genomes
Hematology
Hepatocellular carcinoma
Human health and pathology
Life Sciences
Liver cancer
Plasma
Plasma levels
siRNA
computational biology
coagulation factor
genetics
biomarkers
factor V
Online AccessGet full text
ISSN1538-7933
1538-7836
1538-7836
DOI10.1111/jth.14562

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Abstract Background Factor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation process. Objective To detect novel genetic loci participating to the regulation of FV plasma levels. Methods We conducted the first Genome Wide Association Study on FV plasma levels in a sample of 510 individuals and replicated the main findings in an independent sample of 1156 individuals. Results In addition to genetic variations at the F5 locus, we identified novel associations at the PLXDC2 locus, with the lead PLXDC2 rs927826 polymorphism explaining ~3.7% (P = 7.5 × 10−15 in the combined discovery and replication samples) of the variability of FV plasma levels. In silico transcriptomic analyses in various cell types confirmed that PLXDC2 expression is positively correlated to F5 expression. SiRNA experiments in human hepatocellular carcinoma cell line confirmed the role of PLXDC2 in modulating factor F5 gene expression, and revealed further influences on F2 and F10 expressions. Conclusion Our study identified PLXDC2 as a new molecular player of the coagulation process.
AbstractList Factor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation process.BACKGROUNDFactor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation process.To detect novel genetic loci participating to the regulation of FV plasma levels.OBJECTIVETo detect novel genetic loci participating to the regulation of FV plasma levels.We conducted the first Genome Wide Association Study on FV plasma levels in a sample of 510 individuals and replicated the main findings in an independent sample of 1156 individuals.METHODSWe conducted the first Genome Wide Association Study on FV plasma levels in a sample of 510 individuals and replicated the main findings in an independent sample of 1156 individuals.In addition to genetic variations at the F5 locus, we identified novel associations at the PLXDC2 locus, with the lead PLXDC2 rs927826 polymorphism explaining ~3.7% (P = 7.5 × 10-15 in the combined discovery and replication samples) of the variability of FV plasma levels. In silico transcriptomic analyses in various cell types confirmed that PLXDC2 expression is positively correlated to F5 expression. SiRNA experiments in human hepatocellular carcinoma cell line confirmed the role of PLXDC2 in modulating factor F5 gene expression, and revealed further influences on F2 and F10 expressions.RESULTSIn addition to genetic variations at the F5 locus, we identified novel associations at the PLXDC2 locus, with the lead PLXDC2 rs927826 polymorphism explaining ~3.7% (P = 7.5 × 10-15 in the combined discovery and replication samples) of the variability of FV plasma levels. In silico transcriptomic analyses in various cell types confirmed that PLXDC2 expression is positively correlated to F5 expression. SiRNA experiments in human hepatocellular carcinoma cell line confirmed the role of PLXDC2 in modulating factor F5 gene expression, and revealed further influences on F2 and F10 expressions.Our study identified PLXDC2 as a new molecular player of the coagulation process.CONCLUSIONOur study identified PLXDC2 as a new molecular player of the coagulation process.
Background Factor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation process. Objective To detect novel genetic loci participating to the regulation of FV plasma levels. Methods We conducted the first Genome Wide Association Study on FV plasma levels in a sample of 510 individuals and replicated the main findings in an independent sample of 1156 individuals. Results In addition to genetic variations at the F5 locus, we identified novel associations at the PLXDC2 locus, with the lead PLXDC2 rs927826 polymorphism explaining ~3.7% (P = 7.5 × 10−15 in the combined discovery and replication samples) of the variability of FV plasma levels. In silico transcriptomic analyses in various cell types confirmed that PLXDC2 expression is positively correlated to F5 expression. SiRNA experiments in human hepatocellular carcinoma cell line confirmed the role of PLXDC2 in modulating factor F5 gene expression, and revealed further influences on F2 and F10 expressions. Conclusion Our study identified PLXDC2 as a new molecular player of the coagulation process.
Background Factor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation process. Objective To detect novel genetic loci participating to the regulation of FV plasma levels. Methods We conducted the first Genome Wide Association Study on FV plasma levels in a sample of 510 individuals and replicated the main findings in an independent sample of 1156 individuals. Results In addition to genetic variations at the F5 locus, we identified novel associations at the PLXDC2 locus, with the lead PLXDC2 rs927826 polymorphism explaining ~3.7% (P = 7.5 × 10−15 in the combined discovery and replication samples) of the variability of FV plasma levels. In silico transcriptomic analyses in various cell types confirmed that PLXDC2 expression is positively correlated to F5 expression. SiRNA experiments in human hepatocellular carcinoma cell line confirmed the role of PLXDC2 in modulating factor F5 gene expression, and revealed further influences on F2 and F10 expressions. Conclusion Our study identified PLXDC2 as a new molecular player of the coagulation process.
Factor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation process. To detect novel genetic loci participating to the regulation of FV plasma levels. We conducted the first Genome Wide Association Study on FV plasma levels in a sample of 510 individuals and replicated the main findings in an independent sample of 1156 individuals. In addition to genetic variations at the F5 locus, we identified novel associations at the PLXDC2 locus, with the lead PLXDC2 rs927826 polymorphism explaining ~3.7% (P = 7.5 × 10 in the combined discovery and replication samples) of the variability of FV plasma levels. In silico transcriptomic analyses in various cell types confirmed that PLXDC2 expression is positively correlated to F5 expression. SiRNA experiments in human hepatocellular carcinoma cell line confirmed the role of PLXDC2 in modulating factor F5 gene expression, and revealed further influences on F2 and F10 expressions. Our study identified PLXDC2 as a new molecular player of the coagulation process.
BackgroundFactor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation process.ObjectiveTo detect novel genetic loci participating to the regulation of FV plasma levels.MethodsWe conducted the first Genome Wide Association Study on FV plasma levels in a sample of 510 individuals and replicated the main findings in an independent sample of 1156 individuals.ResultsIn addition to genetic variations at the F5 locus, we identified novel associations at the PLXDC2 locus, with the lead PLXDC2 rs927826 polymorphism explaining ~3.7% (P = 7.5 × 10−15 in the combined discovery and replication samples) of the variability of FV plasma levels. In silico transcriptomic analyses in various cell types confirmed that PLXDC2 expression is positively correlated to F5 expression. SiRNA experiments in human hepatocellular carcinoma cell line confirmed the role of PLXDC2 in modulating factor F5 gene expression, and revealed further influences on F2 and F10 expressions.ConclusionOur study identified PLXDC2 as a new molecular player of the coagulation process.
Author Goumidi, Louisa
Hardy, Lise
Saut, Noémie
Civelek, Mete
Morange, Pierre‐Emmanuel
Ibrahim‐Kosta, Manal
Le Goff, Wilfried
Thibord, Florian
Deleuze, Jean‐François
Pulcrano‐Nicolas, Anne‐Sophie
Eriksson, Per
Trégouët, David‐Alexandre
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Issue 11
Keywords computational biology
coagulation factor
genetics
biomarkers
factor V
Language English
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Snippet Background Factor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation...
Factor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation process. To...
BackgroundFactor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation...
Factor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation...
Background Factor V (FV) is a circulating protein primarily synthesized in the liver, and mainly present in plasma. It is a major component of the coagulation...
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SubjectTerms biomarkers
Coagulation
coagulation factor
Coagulation factors
computational biology
Factor V
Gene expression
Gene loci
Genetic diversity
genetics
Genome-wide association studies
Genomes
Hematology
Hepatocellular carcinoma
Human health and pathology
Life Sciences
Liver cancer
Plasma
Plasma levels
siRNA
Title A Genome Wide Association Study on plasma FV levels identified PLXDC2 as a new modifier of the coagulation process
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fjth.14562
https://www.ncbi.nlm.nih.gov/pubmed/31271701
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https://www.proquest.com/docview/2253304890
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Volume 17
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