| Biography | |
|---|---|
 Prof. Sofia Siest INSERM/University of Lorraine,Nancy, France |
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| Title: VEGF-A, a potential biomarker for systems medicine | |
| Abstract: Vascular endothelial growth factor–A (VEGF–A) is implicated in angiogenesis, lymphangiogenesis, vascular permeability, and haematopoiesis. It is associated with 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. The GWAS was performed in 3,527 healthy participants (Framingham Heart Study) and the most significant results (P <5x10-8) were replicated in 1,727 individuals (STANISLAS Family Study, PIVUS study). Functional transcriptomic analyses were performed in peripheral blood mononuclear cells (PBMCs). Furthermore, in 403 healthy adults the associations between VEGF–A and adhesion/inflammation molecules were tested. Also, associations between VEGF–A and blood lipids were assessed in a discovery (n=1,006) and in a replication population (n=1,145) of healthy individuals. Four polymorphisms (rs6921438, rs4416670, rs6993770, rs10738760) explaining ~50% of VEGF–A heritability were identified. These variants,directly or via gene x 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 rsfurther explaining VEGF–A levels variability and ongoing investigations focus on clinical implementation of the ‘–omics’ determinants of this biomarker. Our integrative strategy resulted to significant results indicating molecular links between VEGF–A and cardio-vascular disease biology and the importance of epistatic and gene x environment interactions. This example illustrates an improved strategy to be applied for every biomarker with high heritability levels, consequently with potential interest in Personalised Medicine, using familial design and the existing biobanks. | |
| Biography: Sofia Siest, PhD, was born in Athens, Greece, where she obtained a diploma of Biology. She received a PhD on Genetic Epidemiology of Cardiovascular Diseases at the University of Nancy, France. She is Director of Research at INSERM since 2001. She has the direction of an INSERM Research Unit in Nancy: INSERM UMR U1122; “Interactions Géne-Environement en Physiopathologie Cardio-Vasculaire” (IGE-PCV) at the University of Lorraine. She has the direction of a Biological Ressources Center (BRC): “Interactions Géne-Environement en Physiopathologie Cardio-Vasculaire” (IGE-PCV) from 2002. She is the scientific director of the STANISLAS Cohort origin project based on 1,006 families followed for 15 years (STANISLAS Family Study, SFS). Dr Sophie Visvikis-Siest’s main research interests are in the domain of public health, Personalised Medicine, prevention, genetic epidemiology, genomics and pharmacogenomics, cardio-vascular diseases, VEGF and inflammation. Most of her publications are based on these topics. She has published more than 350 papers in international scientific committee journals (index h: 50, citations: 11419), 2 patents and gave more than 80 international conferences under invitation. She has a long experience in acquisition and successful execution of public, academic, industrial and EC founded projects. She participates in BBMRI (Biobanking and Biomolecular Resources Research Infrastructure) European Biobanking initiative and is one of the pioneers in Biobanking founded by INSERM and ANR in France. She has a 20-years’ experience in the prevention field by her involvement in the Center of Preventive Medicine in Vandoeuvre-lès-Nancy, France. She is Vice-President of the European Society of Predictive Medicine (EUSPM) from its creation at 2009 (www.euspm.org) and Chair of the meetings division of the European Society of Pharmacogenomics and Theranostics (ESPT) from 2011(www.esptnet.eu). She is involved in the Scientific Organization of several Congresses, Meetings and Courses, in France and abroad and she is also Responsible of her own Meetings named “Santorini Conferences” held every 2 years since 2002 in Santorini, Greece, in the domain of Genomics, Pharmacogenomics and Personalised Medicine. | |
