Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity

Abstract Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family and is involved in bone marrow-derived cell activation, endothelial stimulation and pathological angiogenesis. High levels of PlGF have been observed in several pathological conditions especially in...

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Autores principales:	Daniela Ruggiero, Teresa Nutile, Stefania Nappo, Alfonsina Tirozzi, Celine Bellenguez, Anne-Louise Leutenegger, Marina Ciullo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db608f2b83b445a3b7a858a7e3aa5d45
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spelling	oai:doaj.org-article:db608f2b83b445a3b7a858a7e3aa5d452021-12-02T16:46:35ZGenetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity10.1038/s41598-021-96256-02045-2322https://doaj.org/article/db608f2b83b445a3b7a858a7e3aa5d452021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96256-0https://doaj.org/toc/2045-2322Abstract Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family and is involved in bone marrow-derived cell activation, endothelial stimulation and pathological angiogenesis. High levels of PlGF have been observed in several pathological conditions especially in cancer, cardiovascular, autoimmune and inflammatory diseases. Little is known about the genetics of circulating PlGF levels. Indeed, although the heritability of circulating PlGF levels is around 40%, no studies have assessed the relation between PlGF plasma levels and genetic variants at a genome-wide level. In the current study, PlGF plasma levels were measured in a population-based sample of 2085 adult individuals from three isolated populations of South Italy. A GWAS was performed in a discovery cohort (N = 1600), followed by a de novo replication (N = 468) from the same populations. The meta-analysis of the discovery and replication samples revealed one signal significantly associated with PlGF circulating levels. This signal was mapped to the PlGF co-receptor coding gene NRP1, indicating its important role in modulating the PlGF plasma levels. Two additional signals, at the PlGF receptor coding gene FLT1 and RAPGEF5 gene, were identified at a suggestive level. Pathway and TWAS analyses highlighted genes known to be involved in angiogenesis and immune response, supporting the link between these processes and PlGF regulation. Overall, these data improve our understanding of the genetic variation underlying circulating PlGF levels. This in turn could lead to new preventive and therapeutic strategies for a wide variety of PlGF-related pathologies.Daniela RuggieroTeresa NutileStefania NappoAlfonsina TirozziCeline BellenguezAnne-Louise LeuteneggerMarina CiulloNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniela Ruggiero Teresa Nutile Stefania Nappo Alfonsina Tirozzi Celine Bellenguez Anne-Louise Leutenegger Marina Ciullo Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity
description	Abstract Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family and is involved in bone marrow-derived cell activation, endothelial stimulation and pathological angiogenesis. High levels of PlGF have been observed in several pathological conditions especially in cancer, cardiovascular, autoimmune and inflammatory diseases. Little is known about the genetics of circulating PlGF levels. Indeed, although the heritability of circulating PlGF levels is around 40%, no studies have assessed the relation between PlGF plasma levels and genetic variants at a genome-wide level. In the current study, PlGF plasma levels were measured in a population-based sample of 2085 adult individuals from three isolated populations of South Italy. A GWAS was performed in a discovery cohort (N = 1600), followed by a de novo replication (N = 468) from the same populations. The meta-analysis of the discovery and replication samples revealed one signal significantly associated with PlGF circulating levels. This signal was mapped to the PlGF co-receptor coding gene NRP1, indicating its important role in modulating the PlGF plasma levels. Two additional signals, at the PlGF receptor coding gene FLT1 and RAPGEF5 gene, were identified at a suggestive level. Pathway and TWAS analyses highlighted genes known to be involved in angiogenesis and immune response, supporting the link between these processes and PlGF regulation. Overall, these data improve our understanding of the genetic variation underlying circulating PlGF levels. This in turn could lead to new preventive and therapeutic strategies for a wide variety of PlGF-related pathologies.
format	article
author	Daniela Ruggiero Teresa Nutile Stefania Nappo Alfonsina Tirozzi Celine Bellenguez Anne-Louise Leutenegger Marina Ciullo
author_facet	Daniela Ruggiero Teresa Nutile Stefania Nappo Alfonsina Tirozzi Celine Bellenguez Anne-Louise Leutenegger Marina Ciullo
author_sort	Daniela Ruggiero
title	Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity
title_short	Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity
title_full	Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity
title_fullStr	Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity
title_full_unstemmed	Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity
title_sort	genetics of plgf plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/db608f2b83b445a3b7a858a7e3aa5d45
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Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity

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