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Journal of Biomedical Research | Volume: 29
November 19-20, 2018 | Paris, France
Molecular Biology, Tissue Science and Regenerative Medicine
International Conference on
Joint Event
&
4th World Heart Congress
VEGF-A, a potential biomarker for systems medicine
Sofia Siest
University of Lorraine, France
Vascular endothelial growth factor–A (VEGF–A) is implicated
in angiogenesis, lymphangiogenesis, vascular permeability
and haematopoiesis. It is associatedwith numerous pathologies
including cardio-vascular diseases and several types of cancer.
We specifically developed an integrative systems biology
strategy for clinical improvement of this biomarker.
A high heritability of this trait, 60% was estimated in the
STANISLAS cohort giving us the needed arguments to continue
for a deep characterization of the genetic component of
VEGF–A levels. Therefore, we searched, by a Genome Wide
Association Study (GWAS), the VEGF–A genetic variants and
the inter-connexions of these biomarkers with other disease-
associated molecules in healthy populations. Functional
transcriptomic analyses were performed in peripheral blood
mononuclear cells (PBMCs). Four polymorphisms (rs6921438,
rs4416670, rs6993770, rs10738760) explaining ~50%of VEGF–A
heritability were identified. These variants, directly or via gene
x environment interactions had significant effects on HDL, LDL,
TNF-a, IL-6, E selectin and ICAM-1 plasma levels. SNP rs6993770
was shown to increase VEGF121 mRNA levels and rs4416670
was associated with L-selectin expression.
Recently, thanks to a meta-GWAS, we identified 6 additional
rs further explaining VEGF–A levels variability and ongoing
investigations focus on clinical implementation of the ‘–omics’
determinants of this biomarker.
Our integrative strategy illustrates an improved exemple to
be applied for every biomarker with high heritability levels,
consequently with potential interest in personalised medicine
e:
Molecular Biology & Heart Congress 2018, Volume 29
DOI: 10.4066/biomedicalresearch-C8-023